Share this article on:

Cross-species transmission of simian retroviruses: how and why they could lead to the emergence of new diseases in the human population

Locatelli, Sabrina; Peeters, Martine

doi: 10.1097/QAD.0b013e328350fb68
Editorial Review

The HIV-1 group M epidemic illustrates the extraordinary impact and consequences resulting from a single zoonotic transmission. Exposure to blood or other secretions of infected animals, through hunting and butchering of bushmeat, or through bites and scratches inflicted by pet nonhuman primates (NHPs), represent the most plausible source for human infection with simian immunodeficiency virus (SIV), simian T-cell lymphotropic virus (STLV) and simian foamy virus. The chance for cross-species transmissions could increase when frequency of exposure and retrovirus prevalence is high. According to the most recent data, human exposure to SIV or STLV appears heterogeneous across the African countries surveyed. Exposure is not sufficient to trigger disease: viral and host molecular characteristics and compatibility are fundamental factors to establish infection. A successful species jump is achieved when the pathogen becomes transmissible between individuals within the new host population. To spread efficiently, HIV likely required changes in human behavior. Given the increasing exposure to NHP pathogens through hunting and butchering, it is likely that SIV and other simian viruses are still transmitted to the human population. The behavioral and socio-economic context of the twenty-first century provides favorable conditions for the emergence and spread of new epidemics. Therefore, it is important to evaluate which retroviruses the human population is exposed to and to better understand how these viruses enter, infect, adapt and spread to its new host.

UMI 233, TransVIHMI, Institut de Recherche pour le Développement (IRD) and University of Montpellier 1, Montpellier, France.

Correspondence to Martine Peeters, UMI 233, TransVIHMI IRD, 911 Avenue Agropolis, BP 64501, 34394 Montpellier, Cedex 5, France. Tel: +33 4 6741 6161; fax: +33 4 6741 6146; e-mail:

Received 5 October, 2011

Revised 21 December, 2011

Accepted 3 January, 2012

Back to Top | Article Outline


Emerging infectious diseases (EIDs) are a major threat to human health and in recent decades we observed the rise in new epidemics in the human population. Importantly, the majority of EID events (60.3%) are caused by zoonotic pathogens and more than 70% have their origin in wildlife [1]. AIDS is one of the most threatening infectious diseases with a zoonotic origin to have emerged in the twentieth century. Simian immunodeficiency viruses (SIVs) from chimpanzees and gorillas from west central Africa have crossed the species barrier on at least four occasions, leading to HIV-1 group M, N, O and P in humans [2–6]. HIV-2 group A–H result from at least eight independent transmissions of SIVs infecting sooty mangabeys from west Africa [3,7,8]. These HIV variants have different epidemiological histories and only one, HIV-1 group M, has spread worldwide, with a cumulative number of almost 60 million infections worldwide [9], since the description of the first AIDS cases in the 1980s [10]. Nonhuman primates (NHPs) are also infected with other retroviruses, notably simian T-cell lymphotropic viruses (STLVs), which crossed the species barrier on multiple occasions causing human T-cell lymphotrophic virus (HTLV) infections affecting between 10 and 20 million people around the world. However, only 5% of the HTLV-infected population develops serious health problems [11]. The simian foamy virus (SFV) is ubiquitous among NHPs and seems to infect humans without any consequence for their health [12,13]. Transmission from human to human has not been reported, but this virus represents a valuable tool to determine whether a population is exposed to potentially more dangerous pathogens hosted by NHP. The HIV-1 group M epidemic illustrates the extraordinary impact and consequences, resulting from a single zoonotic transmission. Therefore, it is important to evaluate which retroviruses the human population is exposed to and to better understand how these viruses enter, infect, adapt and spread to its new host. We review here the actual knowledge on retroviral infections in wild NHP and describe some of the factors playing a role in the transmission and emergence of such infections in the human population.

Back to Top | Article Outline

The simian retroviruses: molecular epidemiology, phylogeny and geographical distribution

This review will focus on three simian retroviruses: SIV, STLV and SFV.

Back to Top | Article Outline

Simian immunodeficiency viruses

Evolution and phylogeny of simian immunodeficiency viruses

To date, 45 species of NHPs among the 73 recognized species from Africa showed serological evidence of SIV infection, and in the majority of them, SIV has been confirmed by viral sequence analysis (Table 1) [14–29]. Up to 90% of the NHP species tested were SIV-positive; therefore, we can speculate that, among the remaining approximately 30 species to investigate, the majority could show a positive profile. Interestingly, SIV infection has not been documented in Asian or South American NHPs, although no large surveys have been conducted yet on wild NHP species in these continents. The genetic diversity of NHP lentiviruses is extremely complex and, although each species is infected with a species-specific SIV (Fig. 1), the SIV phylogenetic clusters are only partially superimposable on trees representing phylogenetic relations between NHP hosts. On one hand, there are profiles suggesting correspondence between virus and host phylogeny, as for SIVs infecting the four African green monkey subspecies (Chlorocebus spp.) or SIVs infecting arboreal Cercopithecus species [30,31]. On the other hand, there are SIV phylogenetic trees matching with several NHP species profiles, demonstrating the possibility of cross-species transmissions of SIVs between NHP sharing the same habitat. For example, SIVagm infecting African green monkeys has been transmitted to Patas monkeys in west Africa [32] and to baboons in south Africa [33]. Cross-species transmission followed by recombination between different SIV strains can also occur among NHP species sharing the same habitat, as demonstrated for SIVmus-2 infecting mustached monkeys from Cameroon. This is a virus issued from the recombination between SIVgsn infecting greater spot-nosed monkeys and SIVmus infecting mustached monkeys [34]. SIVcpz infecting chimpanzees is another example of cross-species transmission, followed by recombination between SIVrcm from red-capped mangabeys and SIVgsn from the greater spot-nosed monkeys’ lineage [35]. Chimpanzees were most probably infected with these viruses, while hunting and consuming the monkey flesh. The recombination must have occurred within a chimpanzee and the new virus became the common ancestor of today's SIVcpz lineages, which was subsequently transmitted to gorillas and humans [5]. A single NHP species can also be infected with two different viruses, as in the case of SIVmus-1 and SIVmus-2 in mustached monkeys [34] or, depending on the geographic region the species occupies, as for mandrills, which are infected with SIVmnd-1 south of the Ogooue River and SIVmnd-2 north of the river in Gabon and in Cameroon [36].

Back to Top | Article Outline

Simian immunodeficiency virus molecular epidemiology, prevalence and diagnostic techniques

Despite the fact that SIVs have been identified in 45 different NHP species from Africa, information on prevalence and molecular epidemiology are lacking for most of them (Table 1). The challenge of studying SIV infection in wild NHPs relies on the fact that these endangered populations live in remote forest regions and are difficult to spot and follow. At first, SIV infection tests were conducted using blood drawn from captive animals, either living in zoos, primate centers or kept as pets. Therefore, results on SIV prevalence were far from reflecting the situation of the populations in the wild. It was, thus, important to develop a noninvasive approach and significant efforts have been made to optimize the detection of antibodies and viral RNA in fecal samples, although at lower sensitivities than in blood [37].

Large-scale molecular epidemiological studies were initiated across Africa with this approach, and several thousand fecal samples were collected from chimpanzees to investigate more in detail the origin of HIV-1. These studies revealed a prevalence ranging from 0 up to 35% of SIVcpzPtt and SIVcpzPts in Pan troglodytes troglodytes from west central Africa and in Pan troglodytes schweinfurthii from east Africa [4,38,39]. These studies also showed that SIVcpzPtt strains are significantly more closely related to HIV-1 strains from humans, and that the ancestors of HIV-1 M and N could be traced to distinct chimpanzee communities in south-east and south-central Cameroon [4]. Despite testing of numerous samples, no SIV infection has been detected yet in the other two chimpanzee subspecies, Pan troglodytes ellioti (previously Pan troglodytes vellerosus) and Pan troglodytes verus[4,40–42] (Fig. 2). Another large molecular epidemiological survey, aimed at studying the origins of HIV-1, was conducted across southern Cameroon on fecal samples from wild gorillas. Gorillas are infected with SIVgor and this study showed that the overall SIVgor prevalence was three times smaller than that observed in chimpanzees in the same areas. SIVgor strains form a monophyletic group within the HIV-1/SIVcpzPtt radiation, but they are all most closely related to the HIV-1 O and P groups [5,6,43]. HIV-1 P is most likely of gorilla origin, but the reservoirs of the direct ancestors of HIV-1 O have not been identified yet. The four HIV-1 groups fall within the HIV-1/SIVcpzPtt/SIVgor radiation; therefore, the cross-species transmissions giving rise to HIV-1 occurred most likely in western equatorial Africa, home of P.t. troglodytes chimpanzees and western lowland gorillas (Gorilla gorilla gorilla) (Fig. 2). Noninvasive surveys were also conducted among wild NHP populations in Côte d’Ivoire and the ancestors of the HIV-2 group A and B viruses, responsible for the HIV-2 epidemic in west Africa, were identified in wild sooty mangabey populations in the Tai forest in Côte d’Ivoire, close to the border with Liberia [44]. In general, the knowledge on SIV prevalence and geographic distribution remains limited today, because only a few large-scale studies have been conducted on retroviral infections in wild primate populations. Collecting and analyzing fecal samples is difficult, very labor-intensive in the field and also in the laboratory. It becomes even more challenging when arboreal species are investigated, as illustrated by studies on Colobinae and Cercopithecus species from the Tai forest in Côte d’Ivoire. Moreover, if antibody detection is not possible in fecal samples, as in some Colobus species, screening by viral RNA amplification is necessary [45,46].

An alternative approach to determine the SIV prevalence, and, indirectly, to measure simultaneously the extent of SIV exposure in the human population, is to analyze tissue and/or blood samples collected from NHP bushmeat. The bushmeat trade contributes to the decline of many endangered primate species and it is, therefore, important not to encourage further hunting while collecting samples at the markets. Studies on bushmeat samples from different forest regions in Cameroon and in the Democratic Republic of Congo (DRC) revealed an overall SIV seroprevalence of 3 and 19%, respectively. These studies also showed significantly different prevalence rates per species (0 to >40%), and variations within species according to the sampling site [18,19].

Estimating the SIV prevalence in wild living NHP populations also requires considering the relative specificity and sensitivity of the serological tests available. Early studies relied on HIV screening or confirmatory assays, which are based on cross-reactivity with HIV-1 and/or HIV-2 antigens, which could underestimate the SIV prevalence. Further on, immuno-enzymatic methods (i.e. ELISA) have been developed, targeting specific SIV lineages, to increase the tests sensitivity [18,47–49]. Meanwhile, the number of new SIV lineages as well as the genetic diversity within lineages has increased; therefore, the number of antigens, which needed to be included in the tests, became important. To contain the workload and to limit the amount of biological material, often available at very low quantities, a multiple analyte profiling technology (xMAP) has been adapted to allow a single sample to be tested simultaneously for 35 peptides with similar sensitivities and specificities [19].

Back to Top | Article Outline

Transmission and pathogenicity of simian immunodeficiency virus in the natural host

There is still little information available today on SIV pathogenic properties and on the transmission routes in its natural host. Horizontal transmission by sexual contact or biting, and vertical transmission, has been demonstrated [36,44,50–53].

On the basis of studies on SIVagm and SIVsmm infections in captive African green monkeys and sooty mangabeys [54], and despite active viral replication and high-prevalence levels, SIV infections were until very recently, generally considered nonpathogenic in their natural hosts [55–57]. Progression to AIDS has been observed in a few captive NHP, who lived past the average life span and were infected over long periods. Two mandrills infected with SIVmnd-1 and SIVmnd-2 developed AIDS, after 17 years of SIV infection [58]; a sooty mangabey naturally infected with SIVsmm progressed to AIDS after 18 years and an African green monkey co-infected with SIVagm and STLV was also reported to progress to AIDS [59,60]. The general assumption that all natural SIV infections were harmless has been challenged recently by a study conducted on two habituated populations of chimpanzees (P.t. schweinfurthii) at Gombe National Park in Tanzania. The SIV infectious status was assessed, by analyzing the fecal samples collected on a regular basis for more than 10 years. SIV infection was associated with a 10–16-fold increase in age-corrected risk of death. Fertility was significantly reduced in SIV-positive females, both in terms of their birth rate and the survival of the offspring. Immunohistochemistry and in-situ hybridization of postmortem spleen and lymph node samples showed lower CD4+ T-cell counts in SIV-positive versus SIV-negative individuals. CD4+ T-cell counts and tissue samples strongly resembled the histopathology of human end-stage AIDS patients [61]. Similarly, a recent report on a naturally SIV-infected P.t.troglodytes chimpanzee confiscated in Cameroon in 2003, subspecies in which the ancestors of HIV-1 have been documented, also suggests clinical progression to an AIDS-like disease [62].

Back to Top | Article Outline

Simian T-lymphotrophic viruses

Evolution and phylogeny

To date, simian counterparts, STLV-1–3, have been described for HTLV type 1–3 in humans, and no simian virus analogue to the recently discovered HTLV-4 has been identified yet [63]. Conversely, no human analogue has been reported today for the tentatively identified STLV-5 in a macaque species from Asia [20]. Since the first descriptions of STLV and HTLV around 1980 [64], the virus has infected between 10 and 20 million people worldwide. In contrast to HIV, the majority of HTLV-1 infections remain asymptomatic: about 5% of them are associated with severe diseases, such as adult T-cell leukemia/lymphoma, or inflammatory diseases of the central nervous system, such as the HTLV-1-associated myelopathy/tropical spastic paraparesis [11,65]. HTLV-2 is less pathogenic [66] and no information is available yet for the recently described HTLV-3 and HTLV-4, but viral structure of HTLV-3 suggests a pathogenic potential similar to HTLV- 1 [67,68].

Back to Top | Article Outline

Simian T-lymphotrophic virus molecular epidemiology, prevalence and diagnostic techniques

Although STLV-1 has been documented in more than 30 Old World monkey species and apes from sub-Saharan Africa and Asia, STLV-3 has only been isolated in African monkeys and STLV-2 only in bonobos, an ape species endemic to DRC [20,69–71] (Table 1). Phylogenetic analyses show that STLV-1 and STLV-3 cluster by geography, rather than by host species, and STLV-1 and STLV-3 viruses are interspersed within the different HTLV-1 and HTLV-3 subtypes, suggesting not only multiple cross-species transmissions among NHPs but also from NHPs to humans (Fig. 3a and b) [20,71–75]. Cocirculation of STLV-1 and STLV-3 within the same species, in the same geographic area, has been documented, as well from different STLV-1 and/or STLV-3 subtypes [20–22].

As observed for SIV, prevalence varied according to the species investigated, ranging between 0.0 and 80% [20,23,76]. Eight to 11% of NHP bushmeat samples from Cameroon and DRC, respectively, are infected with STLV [20,22]. Most of the STLV-infected NHPs display a serological profile very close to that observed in humans infected with HTLV, but it is not known to what extent divergent strains cross-react with the antigens currently used. Similarly, STLV prevalence and genetic diversity can be underestimated for the same reasons described for SIV.

Back to Top | Article Outline

Transmission and pathogenicity of simian T-lymphotrophic virus in the natural host

STLV infection within the same species occurs mainly through sexual contact, aggressive behavior and breastfeeding [77–79]. Aggressive behavior and hunting sympatric STLV-infected species seems to be the most plausible route for STLV cross-species transmission [79–81]. STLV-1 has occasionally been associated with malignant lymphoma or leukemia in macaques, baboons, African green monkeys and gorillas [82–88]. A case of STLV-1 transmission between captive heterologous species (from rhesus macaques to baboons) enhanced oncogenicity in the infected animal, whereas this phenomenon was not observed between homologous macaque species residing in the same center [88].

Back to Top | Article Outline

Simian foamy viruses

SFVs are ubiquitous in NHPs and have been identified in a wide variety of primates, including Prosimians, New World and Old World monkeys as well as apes, and each species has been shown to harbor a unique (species-specific) strain of SFV [89]. SFVs are ancient and well adapted viruses that have co-evolved with their NHPs hosts for more than 30 million years [13]. Little is known about the prevalence and transmission patterns of SFV in wild-living primate populations. SFVs are highly prevalent in captive primate populations, with infection rates ranging from 70 to 100% in adult animals [90–93], and free-ranging macaques from Indonesia [94], Thailand, Nepal and Singapore [95]. Recently, using a fecal-based assay, a high SFV infection rate (44–100%) was detected in chimpanzees from west, central and east Africa. Remarkably, all of the 120 newly characterized SFVcpz strains clustered according to their subspecies of origin [96].

The saliva and blood of infected animals are considered the principal routes of SFV transmission [97,98], but SFVcpz sequences were also found in every targeted body compartment of two chimpanzees examined postmortem [99]. Studies in chimpanzees and African green monkeys indicate predominantly horizontal rather than vertical transmission routes [96,97].

There is no human foamy virus, but SFV infections have been reported in persons occupationally exposed to NHPs and in a few hunters in central Africa with no consequence for their health [100–104]. Efficient transmission of SFVs after ape bites, followed by viral persistence, has been reported in central African hunters [104–106]. No SFV epidemic has been documented yet, and the lack of human-to-human SFV transmission represents an informative marker of contact between human and NHPs.

Back to Top | Article Outline

Simian retroviruses: factors and conditions necessary for a successful transmission to humans

Although the conditions and circumstances determining SIV, STLV and SFV transmission from NHPs to humans are not completely elucidated, exposure to blood or other secretions of infected animals, through hunting and butchering of bushmeat, or through bites and scratches inflicted by pet NHPs, represent the most plausible source for human infection (Fig. 4). Direct evidence for such events has been reported recently for STLV and SFV in primate hunters in independent studies in Cameroon and Gabon [101,104,106–108]. SIV antibodies have been detected in humans exposed to NHP, but the viruses could not be amplified by molecular techniques, suggesting only exposure but no replication [36,109]. Persistent presence of antibodies without detectable viral nucleic acids has also been previously observed in a laboratory worker who has been accidentally exposed to blood from a SIV-infected macaque [110].

Factors associated with single cross-species transmission have to be differentiated from those associated with epidemic spread, the latter being a combination of multiple factors. For an animal pathogen to become successful in humans, it must evolve into a pathogen capable of not only infecting humans but of also maintaining long-term human-to-human transmission without the need for re-introduction from the original animal host. Several steps are, thus, necessary for a disease of zoonotic origin to become a pandemic, a topic extensively discussed in several reviews [111,112]. The type and intensity of contacts between the reservoir host (donor) or its viruses and the new host (recipient), the host barrier to infection at the organism or cell level, the viral factors allowing efficient infection in the new host and the determinants of efficient virus spread within the new host population are all factors that mediate the transition from one stage to the next.

Back to Top | Article Outline

Exposure to simian retroviruses

The chance for cross-species transmissions could increase when frequency of exposure and retrovirus prevalence is high. According to the most recent data, human exposure to SIV or STLV appears heterogeneous across the African countries surveyed [18,19,22,76]. For example, SIV prevalence in NHP bushmeat in Cameroon and DRC is 3 and 19%, respectively, but infection rates can vary significantly according to the species tested (0–50%) [18,19]. Interestingly, in Cameroon the lowest prevalence (0–1%) was observed among the most frequently hunted species (>90% of NHP bushmeat). On the contrary, in DRC, the highest prevalence (25%) was reported in the most frequently hunted monkeys (Fig. 5) [18,19]. In wild-living chimpanzee and sooty mangabey populations in which the HIV-1 M, N and HIV-2 A and B ancestors have been described, SIVcpz and SIVsmm prevalence have been measured at about 30 and 50% [4,42,44], respectively, but this is not sufficient to explain why these viruses became the ancestors of HIV-1 group M and HIV-2 group A and B epidemics. This is illustrated by a study reporting a high prevalence of SIVsmm in feral sooty mangabeys in which viruses were closely related to HIV-2 strains described in isolated human cases in rural Sierra Leone and Liberia [113].

Although studies showed that humans in central Africa are exposed to blood and body fluids from a wide variety of NHP species [18,19,101,114], we generally lack data on prevalence in wild-living primates. Given the number of species infected, cross-species transmissions of other retroviruses to humans should be considered. The recently documented transmissions of SFV and STLV highlight the risk for potential emergence of a new SIV into the human population [101,103–105,107,108]. The description in 2009 of HIV-1 group P [6], closely related to SIVgor, in a Cameroonian patient living in France, shows clearly that our knowledge on HIV diversity and possible cross-species transmissions is still incomplete and illustrates how rapidly new viruses can spread today to other continents.

Back to Top | Article Outline

Virus–host compatibility

After exposure and direct contact, the second step for the pathogen to be able to infect the new host is for pathogen and host to be ‘compatible’. Crucial to the ability of a virus to infect hosts is the presence of appropriate receptors on host cells. When receptors are conserved across a range of possible host species, the hosts are likely to be predisposed to infection by viruses using these receptors. SIVwrc infecting western red colobus provides an example on the importance of viral adaptation and host factors in determining a successful cross-species transmission. Overall, 50–80% of them are infected with SIVs [23,45] and, together with mangabeys, they are heavily hunted for bushmeat [115]. However, in contrast to SIVsmm, no SIVwrc cross-species transmission to humans has been documented yet. Moreover, western red colobus represent 80% of animal proteins ingested by the chimpanzee subspecies (P.t.verus) living in the Tai forest in Côte d’Ivoire [116], but no SIVwrc infection could be identified in its predator [117].

Our knowledge on the role of viral and host factors to efficiently infect and adapt to a new host are still incomplete and they are most probably very complex. Several retroviral restriction factors have been identified in humans, APOBEC3G induces lethal hyper mutations in the retroviral genome, Trim5α proteins restrict the incoming viral capsid, tetherin inhibits the release of viral particles (reviewed in [118]) and SAMHD1 is an antiretroviral protein expressed in cells of the myeloid lineage that inhibits an early step of the viral lifecycle [119]. Primate lentiviruses have acquired accessory genes that can antagonize these antiviral host restriction factors: for example, the Vpu protein of the pandemic HIV-1 M strain is able to block the human restriction factor tetherin, whereas HIV-1 O viruses do not [120]. As a consequence, this could have led to a higher replication of HIV-1 M in humans, a better human-to-human transmission and a better epidemic spread of HIV-1 M versus O in the human population [118,121]. The higher pathogenicity of HIV-1 can also be partially explained by the fact that the function of nef, that allows viral persistence in the host while controlling for superactivation of the immune system, is lost in certain SIV lineages and, more precisely, in the ancestors of the HIV-1/SIVcpz lineage in contrast to SIVsmm/HIV-2, where this adaptation is not observed and where the virus is less pathogenic [122,123]. An adaptation of SIVcpz to its new host has been proposed at the Gag-30 position in the p17 region of the gag gene, in which methionine or leucine is present among SIVcpz/SIVgor, whereas all HIV-1 strains harbor an arginine at this position [124]. The lower viral fitness of HIV-2 compared with HIV-1, and of HIV-1 O versus M, could also partially explain the lower prevalence and limited spread of HIV-2 and HIV-1 O [125]. In general, the frequent examples of cross-species transmissions of SIVs and STLVs among NHPs illustrate that retroviruses have the potential to easily adapt to a new host. Moreover, many SIV lineages have the ability to replicate in vitro in human lymphocytes [126–135]. Although important progress has been made to understand the complex interactions between lentiviruses and their host, more comparative studies of humans, NHP and their respective viruses are needed.

Back to Top | Article Outline

Epidemic spread in the new host species

The next step in a successful species jump for the pathogen is to be sufficiently transmissible among individuals within the new host population. To become fully established, HIV likely required also changes in human behavior. The combination between increasing human density in forest areas, urbanization and human migration from rural to urban areas facilitated the spread. Commercial sex and traditional and new medicinal practices were promoting efficient transmission [136–138]. Iatrogenic factors, that is, the use of unsterilized needles in parenteral mass treatment of certain tropical diseases such as sleeping sickness or syphilis may have been responsible for the start of the HIV pandemic from a few isolated cases of infection to a larger reservoir, allowing subsequent sustained human-to-human sexual transmission of HIV [139]. In addition, serial passages of partially adapted SIVs among humans could have produced a series of cumulative mutations sufficient for the emergence of the epidemic HIV strains [136,137]. Also in the USA and Europe, the initial HIV spillover was observed among populations adopting high-risk sexual behavior or IDUs and among people receiving multiple blood transfusions. The presence of sexually transmitted diseases inducing genital ulcers such as herpes simplex virus type 2 enhance the risk of acquiring HIV infection [140] and probably played a role in efficient sexual spread in the early twentieth century [141]. Conversely, male circumcision seems to limit the chance of contracting HIV [142–144]. The combination of some or all of these factors may have contributed more or less effectively to the spread of the virus in certain population groups and geographic areas.

The first AIDS cases have been described around 1980 in the USA [10], but the virus circulated already early in the twentieth century in the human population in central Africa. It has been estimated by molecular clock analysis that the most recent common ancestor of HIV-1 group M exists since about 1908, and two viruses obtained from blood and tissue samples collected in 1959 and 1960 in Kinshasa indicate that HIV-1 M was already spreading among humans in central Africa 20 years before the recognition of the AIDS epidemic [145,146]. Chimpanzees have been hunted for hundred years in central Africa, and SIVcpz, SIVsmm, STLVs or other retroviral cross-species transmissions most likely occurred at multiple occasions. The fact that the HIV-1 M ancestor was isolated in chimpanzees living in south Cameroon, and that the origin of the epidemic was recorded in Kinshasa, the capital city of DRC [147], located at over a thousand kilometers from the HIV-1 M reservoir, highlights the importance of the role of human factors in the epidemic spread. The development of major cities, such as Kinshasa, in Africa, occurred also in the twentieth century [148] and provided most likely an ideal new socio-economic environment, allowing epidemic spread of a sexually transmitted and blood-borne pathogenic agent (Fig. 6).

Back to Top | Article Outline

Simian retroviruses cross-species transmission in the socio-economic context of the twenty-first century

NHPs have been hunted in west and central Africa for millennia and today many people, especially in rural areas, still rely on bushmeat for subsistence. Unfortunately, hunting has shifted to an organized activity, commercial venture, with eruption of the bushmeat crisis in the late 1980s and early 1990s in the Congo Basin [149,150]. Growing urban populations have commercialized the trade and, in the Congo Basin alone, harvest estimates for all species combined range from 1 to 3.4 million metric tons per year [151–154]. The transportation infrastructure between rural and urban areas provided by the logging industry increased exponentially during the second part of the twentieth century [155] and brought roads, trucks, guns and workers with their families into forest areas once far less accessible [156]. The expansion of oil and mining industries also participated in attracting human population to live in tropical forests. Humans are, thus, more and more exposed to simian retroviruses and other pathogens. Armed conflicts also contributed to the increase in the bushmeat trade [157] and led to profound socio-economic changes and internal displacement of human populations [157]. Importantly, high HIV prevalence was reported around logging industries and in displaced population groups [158,159]. In contrast to the early twentieth century, more people with immune deficiency are now exposed to new pathogens, and superinfection with a new SIV could lead to the recombination between HIVs and SIVs, allowing for a potentially more efficient adaptation and replication in the new host. Importantly, cross-species transmissions from NHPs to humans will most likely occur in rural areas, where, even today, access to health services is poor [160]. This means that new epidemic outbreaks, especially regarding diseases with a long incubation period, can still go unrecognized for a long time. In addition, these SIV strains are not recognized by commercial HIV-1/HIV-2 screening assays. Compared with the early twentieth century, travelling between urban and rural areas has significantly increased, and viruses nowadays can reach rapidly new areas with favorable conditions for epidemic spread. In addition, air travel allows pathogens to cross nations and even continents fast, challenging further the ability to control the emergence of diseases.

Back to Top | Article Outline


Prevalence and exposure are among the variables playing a role in the transmission of simian retroviruses to humans, but viral and host molecular characteristics are fundamental factors to establish efficient infection and disease. Given the ongoing and increasing contact between NHP and African populations through hunting and butchering, it is likely that SIV and other simian viruses are still transmitted to humans. Travelling is on the rise, and new viruses can rapidly reach new areas with favorable conditions for epidemic spread. By improving our knowledge about the NHP retroviral reservoir, we will be able to update, adapt and improve the current diagnostic tools. The development of new high-throughput serological and molecular assays, able to identify a wide diversity of simian retroviruses, will allow large-scale studies at the human–primate interface in areas of Africa where the emergence of new zoonotic diseases is likely to occur. By adding the expertise and support of disciplines such as healthcare, social sciences, primatology, biodiversity, economy and mathematics, it will be possible to target better and faster new cross-species transmission hotspots. It will also be important to build a network of high-quality technical and human resources, supporting detection, identification and monitoring of infectious disease, and to ensure that surveillance is linked operationally to an appropriate response.

Back to Top | Article Outline


The authors thank Eric Delaporte for comments on an early version of the manuscript and Mary K. Gonder for the chimpanzee distribution map. Photographs in Figure 4 were kindly provided by Sabrina Locatelli (a, b), Bernadette Abela (c), and Steve Ahuka-Mundeke (d).

S.L. and M.P. wrote the article.

Back to Top | Article Outline

Conflicts of interest

The authors declare they have no conflicts of interest.

Back to Top | Article Outline


1. Jones KE, Patel NG, Levy MA, Storeygard A, Balk D, Gittleman JL, et al. Global trends in emerging infectious diseases. Nature 2008; 451:990–993.
2. Gao F, Bailes E, Robertson DL, Chen Y, Rodenburg CM, Michael SF, et al. Origin of HIV-1 in the chimpanzee Pan troglodytes troglodytes. Nature 1999; 397:436–441.
3. Hahn BH, Shaw GM, De Cock KM, Sharp PM. AIDS as a zoonosis: scientific and public health implications. Science 2000; 287:607–614.
4. Keele BF, Van Heuverswyn F, Li Y, Bailes E, Takehisa J, Santiago ML, et al. Chimpanzee reservoirs of pandemic and nonpandemic HIV-1. Science 2006; 313:523–526.
5. Van Heuverswyn F, Li Y, Neel C, Bailes E, Keele BF, Liu W, et al. Human immunodeficiency viruses: SIV infection in wild gorillas. Nature 2006; 444:164.
6. Plantier JC, Leoz M, Dickerson JE, De Oliveira F, Cordonnier F, Lemée V, et al. A new human immunodeficiency virus derived from gorillas. Nat Med 2009; 15:871–872.
7. Hirsch VM, Olmsted RA, Murphey-Corb M, Purcell RH, Johnson PR. An African primate lentivirus (SIVsm) closely related to HIV-2. Nature 1989; 339:389–392.
8. Damond F, Worobey M, Campa P, Farfara I, Colin G, Matheron S, et al. Identification of a highly divergent HIV type 2 and proposal for a change in HIV type 2 classification. AIDS Res Hum Retroviruses 2004; 20:666–672.
9. UNAIDS report on the global epidemic 2010. Available at [Accessed October 2011]
10. First report of AIDS. Centers for Disease Control and Prevention. Pneumocystis pneumonia. Morbidity, Mortality Weekly Report (MMWR) 1981; 30:250–252.
11. Gessain A. Human retrovirus HTLV-1: descriptive and molecular epidemiology, origin, evolution, diagnosis and associated diseases.Bull Soc Pathol Exot 2011; 104:167–180.
12. Heneine W, Schweizer M, Sandstrom P, Folks T. Human infection with foamy viruses. Curr Top Microbiol Immunol 2003; 277:181–196.
13. Switzer WM, Salemi M, Shanmugam V, Gao F, Cong ME, Kuiken C, et al. Ancient co-speciation of simian foamy viruses and primates. Nature 2005; 434:376–380.
14. van de Woude S, Apetrei C. Going wild: lessons from naturally occurring T-lymphotropic lentiviruses. Clin Microbiol Rev 2006; 19:728–762.
15. Van Heuverswyn F, Peeters M. The origins of HIV and implications for the global epidemic. Curr Infect Dis Rep 2007; 9:338–346.
16. Worobey M, Telfer P, Souquiere S, Hunter M, Coleman CA, Metzger MJ, et al. Island biogeography reveals the deep history of SIV. Science 2010; 329:1487.
17. Etienne L, Delaporte E, Peeters M. Tibayrenc M. Origin and emergence of HIV/AIDS. Genetics and evolution of infectious diseases. London, UK:Elsevier; 2011. 689–710.
18. Aghokeng AF, Ayouba A, Mpoudi-Ngole E, Loul S, Liegeois F, Delaporte E, et al. Extensive survey on the prevalence and genetic diversity of SIVs in primate bushmeat provides insights into risks for potential new cross-species transmissions. Infect Genet Evol 2010; 10:386–396.
19. Ahuka-Mundeke S, Ayouba A, Mbala-Kingebeni P, Liegeois F, Esteban A, Lunguya-Metila O, et al. A novel multiplexed HIV/SIV antibody detection assay identified new simian immunodeficiency viruses in primate bushmeat in the Democraphic Republic of Congo. Emerg Infect Dis 2011; 17:2277–2286.
20. Liegeois F, Lafay B, Switzer WM, Locatelli S, Mpoudi-Ngole E, Loul S, et al. Identification and molecular characterization of new STLV-1 and STLV-3 strains in wild-caught nonhuman primates in Cameroon. Virology 2008; 371:405–417.
21. Courgnaud V, Van Dooren S, Liegeois F, Pourrut X, Abela B, Loul S, et al. Simian T-cell leukemia virus (STLV) infection in wild primate populations in Cameroon: evidence for dual STLV type 1 and type 3 infection in agile mangabeys (Cercocebus agilis). J Virol 2004; 78:4700–4709.
22. Ahuka-Mundeke S, Mbala-Kingebeni P, Liegeois F, Ayouba A, Lunguya-Metila O, Demba D, et al.Identification and molecular characterization of new simian T cell lymphotropic viruses in nonhuman primates bushmeat from the Democratic Republic of Congo.AIDS Res Hum Retroviruses 2011; 27 [Epub ahead of print].
23. Leendertz SA, Junglen S, Hedemann C, Goffe A, Calvignac S, Boesch C, et al. High prevalence, coinfection rate, and genetic diversity of retroviruses in wild red colobus monkeys (Piliocolobus badius badius) in Tai National Park, Côte d’Ivoire. J Virol 2010; 84:7427–7436.
24. Saksena NK, Herve V, Durand JP, Leguenno B, Diop OM, Digouette JP, et al. Seroepidemiologic, molecular, and phylogenetic analyses of simian T-cell leukemia viruses (STLV-I) from various naturally infected monkey species from central and western Africa. Virology 1994; 198:297–310.
25. Nerrienet E, Meertens L, Kfutwah A, Foupouapouognigni Y, Gessain A. Molecular epidemiology of simian T-lymphotropic virus (STLV) in wild-caught monkeys and apes from Cameroon: a new STLV-1, related to human T-lymphotropic virus subtype F, in a Cercocebus agilis. J Gen Virol 2001; 82:2973–2977.
26. Takemura T, Yamashita M, Shimada MK, Ohkura S, Shotake T, Ikeda M, et al. High prevalence of simian T-lymphotropic virus type L in wild ethiopian baboons. J Virol 2002; 76:1642–1648.
27. Leendertz FH, Boesch C, Ellerbrok H, Rietschel W, Couacy-Hymann E, Pauli G. Noninvasive testing reveals a high prevalence of simian T-lymphotropic virus type 1 antibodies in wild adult chimpanzees of the Tai National Park, Cote d’Ivoire. J Gen Virol 2004; 85:3305–3312.
28. Traina-Dorge VL, Lorino R, Gormus BJ, Metzger M, Telfer P, Richardson D, et al. Molecular epidemiology of simian T-cell lymphotropic virus type 1 in wild and captive sooty mangabeys. J Virol 2005; 79:2541–2548.
29. Goldberg TL, Sintasath DM, Chapman CA, Cameron KM, Karesh WB, Tang S, et al. Coinfection of Ugandan red colobus (Procolobus [Piliocolobus] rufomitratus tephrosceles) with novel, divergent delta-, lenti-, and spumaretroviruses. J Virol 2009; 83:11318–11329.
30. Bibollet-Ruche F, Bailes E, Gao F, Pourrut X, Barlow KL, Clewley JP, et al. New simian immunodeficiency virus infecting De Brazza's monkeys (Cercopithecus neglectus): evidence for a cercopithecus monkey virus clade. J Virol 2004; 78:7748–7762.
31. Wertheim JO, Worobey M. A challenge to the ancient origin of SIVagm based on African green monkey mitochondrial genomes. PLoS Pathog 2007; 3:e95.
32. Bibollet-Ruche F, Galat-Luong A, Cuny G, Sarni-Manchado P, Galat G, Durand JP, et al. Simian immunodeficiency virus infection in a patas monkey (Erythrocebus patas): evidence for cross-species transmission from African green monkeys (Cercopithecus aethiops sabaeus) in the wild. J Gen Virol 1996; 77:773–781.
33. van Rensburg EJ, Engelbrecht S, Mwenda J, Laten JD, Robson BA, Stander T, et al. Simian immunodeficiency viruses (SIVs) from eastern and southern Africa: detection of a SIVagm variant from a chacma baboon. J Gen Virol 1998; 79:1809–1814.
34. Aghokeng AF, Bailes E, Loul S, Courgnaud V, Mpoudi-Ngole E, Sharp PM, et al. Full-length sequence analysis of SIVmus in wild populations of mustached monkeys (Cercopithecus cephus) from Cameroon provides evidence for two co-circulating SIVmus lineages. Virology 2007; 360:407–418.
35. Bailes E, Gao F, Bibollet-Ruche F, Courgnaud V, Peeters M, Marx PA, et al. Hybrid origin of SIV in chimpanzees. Science 2003; 300:1713.
36. Souquiere S, Bibollet-Ruche F, Robertson DL, Makuwa M, Apetrei C, Onanga R, et al. Wild Mandrillus sphinx are carriers of two types of lentivirus. J Virol 2001; 75:7086–7096.
37. Santiago ML, Lukasik M, Kamenya S, Li Y, Bibollet-Ruche F, Bailes E, et al. Foci of endemic simian immunodeficiency virus infection in wild-living eastern chimpanzees (Pan troglodytes schweinfurthii). J Virol 2003; 77:7545–7562.
38. Li Y, Ndjango J-B, Learn G, Robertson J, Takehisa J, Bibollet-Ruche F, et al.Molecular epidemiology of SIV in eastern chimpanzees and gorillas. In: 17th Conference on Retroviruses and Opportunistic Infections; 2010; San Francisco, California.
39. Rudicell RS, Piel AK, Stewart F, Moore DL, Learn GH, Li Y, et al. High prevalence of simian immunodeficiency virus infection in a community of Savanna chimpanzees. J Virol 2011; 85:9918–9928.
40. Prince AM, Brotman B, Lee DH, Andrus L, Valinsky J, Marx P. Lack of evidence for HIV type 1-related SIVcpz infection in captive and wild chimpanzees (Pan troglodytes verus) in west Africa. AIDS Res Hum Retroviruses 2002; 18:657–660.
41. Switzer WM, Parekh B, Shanmugam V, Bhullar V, Phillips S, Ely JJ, et al. The epidemiology of simian immunodeficiency virus infection in a large number of wild- and captive-born chimpanzees: evidence for a recent introduction following chimpanzee divergence. AIDS Res Hum Retroviruses 2005; 21:335–342.
42. Van Heuverswyn F, Li Y, Bailes E, Neel C, Lafay B, Keele BF, et al. Genetic diversity and phylogeographic clustering of SIVcpzPtt in wild chimpanzees in Cameroon. Virology 2007; 368:155–171.
43. Neel C, Etienne L, Li Y, Takehisa J, Rudicell RS, Bass IN, et al. Molecular epidemiology of simian immunodeficiency virus infection in wild-living gorillas. J Virol 2010; 84:1464–1476.
44. Santiago ML, Range F, Keele BF, Li Y, Bailes E, Bibollet-Ruche F, et al. Simian immunodeficiency virus infection in free-ranging sooty mangabeys (Cercocebus atys atys) from the Tai Forest, Cote d’Ivoire: implications for the origin of epidemic human immunodeficiency virus type 2. J Virol 2005; 79:12515–12527.
45. Locatelli S, Liegeois F, Lafay B, Roeder AD, Bruford MW, Formenty P, et al. Prevalence and genetic diversity of simian immunodeficiency virus infection in wild-living red colobus monkeys (Piliocolobus badius badius) from the Tai forest, Côte d’Ivoire SIVwrc in wild-living western red colobus monkeys. Infect Genet Evol 2008; 8:1–14.
46. Locatelli S, Roeder AD, Bruford MW, Noë R, Delaporte E, Peeters M. Lack of evidence of simian immunodeficiency virus infection among nonhuman primates in Tai National Park, Cote d’Ivoire: limitations of noninvasive methods and SIV diagnostic tools for studies of primate retroviruses. Int J Primatol 2011; 32:288–307.
47. Simon F, Souquiere S, Damond F, Kfutwah A, Makuwa M, Leroy E, et al. Synthetic peptide strategy for the detection of and discrimination among highly divergent primate lentiviruses. AIDS Res Hum Retroviruses 2001; 17:937–952.
48. Ndongmo CB, Switzer WM, Pau CP, Zeh C, Schaefer A, Pieniazek D, et al. New multiple antigenic peptide-based enzyme immunoassay for detection of simian immunodeficiency virus infection in nonhuman primates and humans. J Clin Microbiol 2004; 42:5161–5169.
49. Aghokeng AF, Liu W, Bibollet-Ruche F, Loul S, Mpoudi-Ngole E, Laurent C, et al. Widely varying SIV prevalence rates in naturally infected primate species from Cameroon. Virology 2006; 345:174–189.
50. Cooper R, Feistner A, Evans S, Tsujimoto H, Hayami M. A lack of evidence of sexual transmission of a simian immunodeficiency agent in a semifree-ranging group of mandrills. AIDS 1989; 3:764.
51. Estaquier J, Peeters M, Bedjabaga L, Honore C, Bussi P, Dixson A, et al. Prevalence and transmission of simian immunodeficiency virus and simian T-cell leukemia virus in a semi-free-range breeding colony of mandrills in Gabon. AIDS 1991; 5:1385–1386.
52. Phillips-Conroy JE, Jolly CJ, Petros B, Allan JS, Desrosiers RC. Sexual transmission of SIVagm in wild grivet monkeys. J Med Primatol 1994; 23:1–7.
53. Otsyula M, Yee J, Jennings M, Suleman M, Gettie A, Tarara R, et al. Prevalence of antibodies against simian immunodeficiency virus (SIV) and simian T-lymphotropic virus (STLV) in a colony of nonhuman primates in Kenya, east Africa. Ann Trop Med Parasitol 1996; 90:65–70.
54. Silvestri G, Paiardini M, Pandrea I, Lederman MM, Sodora DL. Understanding the benign nature of SIV infection in natural hosts. J Clin Invest 2007; 117:3148–3154.
55. Rey-Cuille MA, Berthier JL, Bomsel-Demontoy MC, Chaduc Y, Montagnier L, Hovanessian AG, et al. Simian immunodeficiency virus replicates to high levels in sooty mangabeys without inducing disease. J Virol 1998; 72:3872–3886.
56. Pandrea I, Sodora DL, Silvestri G, Apetrei C. Into the wild: simian immunodeficiency virus (SIV) infection in natural hosts. Trends Immunol 2008; 29:419–428.
57. Pandrea I, Apetrei C. Where the wild things are: pathogenesis of SIV infection in African nonhuman primate hosts. Curr HIV/AIDS Rep 2010; 7:28–36.
58. Pandrea I, Onanga R, Rouquet P, Bourry O, Ngari P, Wickings EJ, et al. Chronic SIV infection ultimately causes immunodeficiency in African nonhuman primates. AIDS 2001; 15:2461–2462.
59. Traina-Dorge V, Blanchard J, Martin L, Murphey-Corb M. Immunodeficiency and lymphoproliferative disease in an African green monkey dually infected with SIV and STLV-I. AIDS Res Hum Retroviruses 1992; 8:97–100.
60. Ling B, Apetrei C, Pandrea I, Veazey RS, Lackner AA, Gormus B, et al. Classic AIDS in a sooty mangabey after an 18-year natural infection. J Virol 2004; 78:8902–8908.
61. Keele BF, Jones JH, Terio KA, Estes JD, Rudicell RS, Wilson ML, et al. Increased mortality and AIDS-like immunopathology in wild chimpanzees infected with SIVcpz. Nature 2009; 460:515–519.
62. Etienne L, Nerrienet E, LeBreton M, Bibila GT, Foupouapouognigni Y, Rousset D, et al. Characterization of a new simian immunodeficiency virus strain in a naturally infected Pan troglodytes troglodytes chimpanzee with AIDS related symptoms. Retrovirology 2011; 8:4.
63. Mahieux R, Gessain A. HTLV-3/STLV-3 and HTLV-4 viruses: discovery, epidemiology, serology and molecular aspects. Viruses 2011; 3:1074–1090.
64. Poiesz BJ, Ruscetti FW, Gazdar AF, Bunn PA, Minna JD, Gallo RC. Detection and isolation of type C retrovirus particles from fresh and cultured lymphocytes of a patient with cutaneous T-cell lymphoma. Proc Natl Acad Sci U S A 1980; 77:7415–7419.
65. Verdonck K, Gonzalez E, Van Dooren S, Vandamme AM, Vanham G, Gotuzzo E. Human T-lymphotropic virus 1: recent knowledge about an ancient infection. Lancet Infect Dis 2007; 7:266–281.
66. Feuer G, Green PL. Comparative biology of human T-cell lymphotropic virus type 1 (HTLV-1) and HTLV-2. Oncogene 2005; 24:5996–6004.
67. Calattini S, Chevalier SA, Duprez R, Afonso P, Froment A, Gessain A, et al. Human T-cell lymphotropic virus type 3: complete nucleotide sequence and characterization of the human tax3 protein. J Virol 2006; 80:9876–9888.
68. Switzer WM, Salemi M, Qari SH, Jia H, Gray RR, Katzourakis A, et al. Ancient, independent evolution and distinct molecular features of the novel human T-lymphotropic virus type 4. Retrovirology 2009; 6:9.
69. Vandamme AM, Salemi M, Desmyter J. The simian origins of the pathogenic human T-cell lymphotropic virus type I. Trends Microbiol 1998; 6:477–483.
70. Van Brussel M, Salemi M, Liu HF, Goubau P, Desmyter J, Vandamme AM. The discovery of two new divergent STLVs has implications for the evolution and epidemiology of HTLVs. Rev Med Virol 1999; 9:155–170.
71. Van Dooren S, Verschoor EJ, Fagrouch Z, Vandamme AM. Phylogeny of primate T lymphotropic virus type 1 (PTLV-1) including various new Asian and African nonhuman primate strains. Infect Genet Evol 2007; 7:374–381.
72. Song KJ, Nerurkar VR, Saitou N, Lazo A, Blakeslee JR, Miyoshi I, et al. Genetic analysis and molecular phylogeny of simian T-cell lymphotropic virus type I: evidence for independent virus evolution in Asia and Africa. Virology 1994; 199:56–66.
73. Slattery JP, Franchini G, Gessain A. Genomic evolution, patterns of global dissemination, and interspecies transmission of human and simian T-cell leukemia/lymphotropic viruses. Genome Res 1999; 9:525–540.
74. Gessain A, Mahieux R. Epidemiology, origin and genetic diversity of HTLV-1 retrovirus and STLV-1 simian affiliated retrovirus. Bull Soc Pathol Exot 2000; 93:163–171.
75. Junglen S, Hedemann C, Ellerbrok H, Pauli G, Boesch C, Leendertz FH. Diversity of STLV-1 strains in wild chimpanzees (Pan troglodytes verus) from Cote d’Ivoire. Virus Res 2010; 150:143–147.
76. Sintasath DM, Wolfe ND, Lebreton M, Jia H, Garcia AD, Le Doux-Diffo J, et al. Simian T-lymphotropic virus diversity among nonhuman primates, Cameroon. Emerg Infect Dis 2009; 15:175–184.
77. Fultz PN, Gordon TP, Anderson DC, McClure HM. Prevalence of natural infection with simian immunodeficiency virus and simian T-cell leukemia virus type I in a breeding colony of sooty mangabey monkeys. AIDS 1990; 4:619–625.
78. Georges-Courbot MC, Moisson P, Leroy E, Pingard AM, Nerrienet E, Dubreuil G, et al. Occurrence and frequency of transmission of naturally occurring simian retroviral infections (SIV, STLV, and SRV) at the CIRMF Primate Center, Gabon. J Med Primatol 1996; 25:313–326.
79. Niphuis H, Verschoor EJ, Bontjer I, Peeters M, Heeney JL. Reduced transmission and prevalence of simian T-cell lymphotropic virus in a closed breeding colony of chimpanzees (Pan troglodytes verus). J Gen Virol 2003; 84:615–620.
80. Nerrienet E, Amouretti X, Muller-Trutwin MC, Poaty-Mavoungou V, Bedjebaga I, Nguyen HT, et al. Phylogenetic analysis of SIV and STLV type I in mandrills (Mandrillus sphinx): indications that intracolony transmissions are predominantly the result of male-to-male aggressive contacts. AIDS Res Hum Retroviruses 1998; 14:785–796.
81. Leendertz FH, Junglen S, Boesch C, Formenty P, Couacy-Hymann E, Courgnaud V, et al. High variety of different simian T-cell leukemia virus type 1 strains in chimpanzees (Pan troglodytes verus) of the Tai National Park, Côte d’Ivoire. J Virol 2004; 78:4352–4356.
82. Homma T, Kanki PJ, King NW Jr, Hunt RD, O’Connell MJ, Letvin NL, et al. Lymphoma in macaques: association with virus of human T lymphotrophic family. Science 1984; 225:716–718.
83. Lee RV, Prowten AW, Satchidanand SK, Srivastava BI. Non-Hodgkin's lymphoma and HTLV-1 antibodies in a gorilla. N Engl J Med 1985; 312:118–119.
84. Sakakibara I, Sugimoto Y, Sasagawa A, Honjo S, Tsujimoto H, Nakamura H, et al. Spontaneous malignant lymphoma in an African green monkey naturally infected with simian T-lymphotropic virus (STLV). J Med Primatol 1986; 15:311–318.
85. Blakeslee JR Jr, McClure HM, Anderson DC, Bauer RM, Huff LY, Olsen RG. Chronic fatal disease in gorillas seropositive for simian T-lymphotropic virus I antibodies. Cancer Lett 1987; 37:1–6.
86. Tsujimoto H, Noda Y, Ishikawa K, Nakamura H, Fukasawa M, Sakakibara I, et al. Development of adult T-cell leukemia-like disease in African green monkey associated with clonal integration of simian T-cell leukemia virus type I. Cancer Res 1987; 47:269–274.
87. McCarthy TJ, Kennedy JL, Blakeslee JR, Bennett BT. Spontaneous malignant lymphoma and leukemia in a simian T-lymphotropic virus type I (STLV-I) antibody positive olive baboon. Lab Anim Sci 1990; 40:79–81.
88. Voevodin A, Samilchuk E, Schatzl H, Boeri E, Franchini G. Interspecies transmission of macaque simian T-cell leukemia/lymphoma virus type 1 in baboons resulted in an outbreak of malignant lymphoma. J Virol 1996; 70:1633–1639.
89. Broussard SR, Comuzzie AG, Leighton KL, Leland MM, Whitehead EM, Allan JS. Characterization of new simian foamy viruses from African nonhuman primates. Virology 1997; 237:349–359.
90. Hussain AI, Shanmugam V, Bhullar VB, Beer BE, Vallet D, Gautier-Hion A, et al. Screening for simian foamy virus infection by using a combined antigen western blot assay: evidence for a wide distribution among Old World primates and identification of four new divergent viruses. Virology 2003; 309:248–257.
91. Calattini S, Nerrienet E, Mauclere P, Georges-Courbot MC, Saib A, Gessain A. Natural simian foamy virus infection in wild-caught gorillas, mandrills and drills from Cameroon and Gabon. J Gen Virol 2004; 85:3313–3317.
92. Calattini S, Nerrienet E, Mauclere P, Georges-Courbot MC, Saib A, Gessain A. Detection and molecular characterization of foamy viruses in central African chimpanzees of the Pan troglodytes troglodytes and Pan troglodytes vellerosus subspecies. J Med Primatol 2006; 35:59–66.
93. Calattini S, Wanert F, Thierry B, Schmitt C, Bassot S, Saib A, et al. Modes of transmission and genetic diversity of foamy viruses in a Macaca tonkeana colony. Retrovirology 2006; 3:23.
94. Engel G, Hungerford LL, Jones-Engel L, Travis D, Eberle R, Fuentes A, et al. Risk assessment: a model for predicting cross-species transmission of simian foamy virus from macaques (M. fascicularis) to humans at a monkey temple in Bali, Indonesia. Am J Primatol 2006; 68:934–948.
95. Jones-Engel L, Engel GA, Schillaci MA, Rompis A, Putra A, Suaryana KG, et al. Primate-to-human retroviral transmission in Asia. Emerg Infect Dis 2005; 11:1028–1035.
96. Liu W, Worobey M, Li Y, Keele BF, Bibollet-Ruche F, Guo Y, et al. Molecular ecology and natural history of simian foamy virus infection in wild-living chimpanzees. PLoS Pathog 2008; 4:e1000097.
97. Falcone V, Leupold J, Clotten J, Urbanyi E, Herchenroder O, Spatz W, et al. Sites of simian foamy virus persistence in naturally infected African green monkeys: latent provirus is ubiquitous, whereas viral replication is restricted to the oral mucosa. Virology 1999; 257:7–14.
98. Murray SM, Linial ML. Foamy virus infection in primates. J Med Primatol 2006; 35:225–235.
99. Morozov VA, Leendertz FH, Junglen S, Boesch C, Pauli G, Ellerbrok H. Frequent foamy virus infection in free-living chimpanzees of the Tai National Park (Côte d’Ivoire). J Gen Virol 2009; 90:500–506.
100. Switzer WM, Bhullar V, Shanmugam V, Cong ME, Parekh B, Lerche NW, et al. Frequent simian foamy virus infection in persons occupationally exposed to nonhuman primates. J Virol 2004; 78:2780–2789.
101. Wolfe ND, Switzer WM, Carr JK, Bhullar VB, Shanmugam V, Tamoufe U, et al. Naturally acquired simian retrovirus infections in central African hunters. Lancet 2004; 363:932–937.
102. Boneva RS, Switzer WM, Spira TJ, Bhullar VB, Shanmugam V, Cong ME, et al. Clinical and virological characterization of persistent human infection with simian foamy viruses. AIDS Res Hum Retroviruses 2007; 23:1330–1337.
103. Switzer WM, Garcia AD, Yang C, Wright A, Kalish ML, Folks TM, et al. Coinfection with HIV-1 and simian foamy virus in west central Africans. J Infect Dis 2008; 197:1389–1393.
104. Betsem E, Rua R, Tortevoye P, Froment A, Gessain A. Frequent and recent human acquisition of simian foamy viruses through apes’ bites in central Africa. PLoS Pathog 2011; 7:e1002306.
105. Calattini S, Betsem EB, Froment A, Mauclere P, Tortevoye P, Schmitt C, et al. Simian foamy virus transmission from apes to humans, rural Cameroon. Emerg Infect Dis 2007; 13:1314–1320.
106. Mouinga-Ondeme A, Caron M, Nkoghe D, Telfer P, Marx P, Saib A, et al.Cross-species transmission of simian foamy virus to humans in rural Gabon, central Africa.J Virol 2012; 86:1255–1260.
107. Wolfe ND, Heneine W, Carr JK, Garcia AD, Shanmugam V, Tamoufe U, et al. Emergence of unique primate T-lymphotropic viruses among central African bushmeat hunters. Proc Natl Acad Sci U S A 2005; 102:7994–7999.
108. Zheng H, Wolfe ND, Sintasath DM, Tamoufe U, Lebreton M, Djoko CF, et al. Emergence of a novel and highly divergent HTLV-3 in a primate hunter in Cameroon. Virology 2010; 401:137–145.
109. Kalish ML, Wolfe ND, Ndongmo CB, McNicholl J, Robbins KE, Aidoo M, et al. Central African hunters exposed to simian immunodeficiency virus. Emerg Infect Dis 2005; 11:1928–1930.
110. Khabbaz RF, Heneine W, George JR, Parekh B, Rowe T, Woods T, et al. Brief report: infection of a laboratory worker with simian immunodeficiency virus. N Engl J Med 1994; 330:172–177.
111. Parrish CR, Holmes EC, Morens DM, Park EC, Burke DS, Calisher CH, et al. Cross-species virus transmission and the emergence of new epidemic diseases. Microbiol Mol Biol Rev 2008; 72:457–470.
112. Wolfe ND, Dunavan CP, Diamond J. Origins of major human infectious diseases. Nature 2007; 447:279–283.
113. Chen Z, Telfer P, Gettie A, Reed P, Zhang L, Ho DD, et al. Genetic characterization of new west African simian immunodeficiency virus SIVsm: geographic clustering of household-derived SIV strains with human immunodeficiency virus type 2 subtypes and genetically diverse viruses from a single feral sooty mangabey troop. J Virol 1996; 70:3617–3627.
114. Peeters M, Courgnaud V, Abela B, Auzel P, Pourrut X, Bibollet-Ruche F, et al. Risk to human health from a plethora of simian immunodeficiency viruses in primate bushmeat. Emerg Infect Dis 2002; 8:451–457.
115. Refisch J, Koné I. Impact of commercial hunting on monkey populations in the Tai region, Cote d’Ivoire. Biotropica 2005; 37:136–144.
116. Boesch C. Chimpanzees-red colobus monkeys: a predator-prey system.Behaviour 1994; 47:1135–1148.
117. Leendertz SA, Locatelli S, Boesch C, Kucherer C, Formenty P, Liegeois F, et al. No evidence for transmission of SIVwrc from western red colobus monkeys (Piliocolobus badius badius) to wild west African chimpanzees (Pan troglodytes verus) despite high exposure through hunting. BMC Microbiol 2011; 11:24–33.
118. Kirchhoff F. Immune evasion and counteraction of restriction factors by HIV-1 and other primate lentiviruses. Cell Host Microbe 2010; 8:55–67.
119. Laguette N, Sobhian B, Casartelli N, Ringeard M, Chable-Bessia C, Segeral E, et al. SAMHD1 is the dendritic- and myeloid-cell-specific HIV-1 restriction factor counteracted by Vpx. Nature 2011; 474:654–657.
120. Sauter D, Schindler M, Specht A, Landford WN, Munch J, Kim KA, et al. Tetherin-driven adaptation of Vpu and Nef function and the evolution of pandemic and nonpandemic HIV-1 strains. Cell Host Microbe 2009; 6:409–421.
121. Gupta RK, Towers GJ. A tail of Tetherin: how pandemic HIV-1 conquered the world. Cell Host Microbe 2009; 6:393–395.
122. Schindler M, Munch J, Kutsch O, Li H, Santiago ML, Bibollet-Ruche F, et al. Nef-mediated suppression of T cell activation was lost in a lentiviral lineage that gave rise to HIV-1. Cell 2006; 125:1055–1067.
123. Sauter D, Kirchhoff F. Tetherin antagonism by primate lentiviral Nef proteins.Curr HIV Res 2011; 9:514–523.
124. Wain LV, Bailes E, Bibollet-Ruche F, Decker JM, Keele BF, Van Heuverswyn F, et al. Adaptation of HIV-1 to its human host. Mol Biol Evol 2007; 24:1853–1860.
125. Arien KK, Abraha A, Quinones-Mateu ME, Kestens L, Vanham G, Arts EJ. The replicative fitness of primary human immunodeficiency virus type 1 (HIV-1) group M, HIV-1 group O, and HIV-2 isolates. J Virol 2005; 79:8979–8990.
126. Peeters M, Honore C, Huet T, Bedjabaga L, Ossari S, Bussi P, et al. Isolation and partial characterization of an HIV-related virus occurring naturally in chimpanzees in Gabon. AIDS 1989; 3:625–630.
127. Peeters M, Fransen K, Delaporte E, Van den Haesevelde M, Gershy-Damet GM, Kestens L, et al. Isolation and characterization of a new chimpanzee lentivirus (simian immunodeficiency virus isolate cpz-ant) from a wild-captured chimpanzee. AIDS 1992; 6:447–451.
128. Peeters M, Janssens W, Fransen K, Brandful J, Heyndrickx L, Koffi K, et al. Isolation of simian immunodeficiency viruses from two sooty mangabeys in Côte d’Ivoire: virological and genetic characterization and relationship to other HIV type 2 and SIVsm/mac strains. AIDS Res Hum Retroviruses 1994; 10:1289–1294.
129. Beer BE, Bailes E, Goeken R, Dapolito G, Coulibaly C, Norley SG, et al. Simian immunodeficiency virus (SIV) from sun-tailed monkeys (Cercopithecus solatus): evidence for host-dependent evolution of SIV within the C. lhoesti superspecies. J Virol 1999; 73:7734–7744.
130. Hirsch VM, Campbell BJ, Bailes E, Goeken R, Brown C, Elkins WR, et al. Characterization of a novel simian immunodeficiency virus (SIV) from L’Hoest monkeys (Cercopithecus l’hoesti): implications for the origins of SIVmnd and other primate lentiviruses. J Virol 1999; 73:1036–1045.
131. Owen SM, Masciotra S, Novembre F, Yee J, Switzer WM, Ostyula M, et al. Simian immunodeficiency viruses of diverse origin can use CXCR4 as a coreceptor for entry into human cells. J Virol 2000; 74:5702–5708.
132. Beer BE, Foley BT, Kuiken CL, Tooze Z, Goeken RM, Brown CR, et al. Characterization of novel simian immunodeficiency viruses from red-capped mangabeys from Nigeria (SIVrcmNG409 and -NG411). J Virol 2001; 75:12014–12027.
133. Poaty-Mavoungou V, Onanga R, Bedjabaga I, Mavoungou E. Simian immunodeficiency virus from mandrill (Mandrillus sphinx) SIVmnd experimentally infects human and nonhuman primate cells. Microbes Infect 2001; 3:599–610.
134. Nerrienet E, Apetrei C, Foupouapouognigni Y, Ling B, Luckay A, Chakrabarti L, et al.New primate lentivirus from agile monkeys (Cercocebus agilis) suggests a host-dependent evolution within mangabeys in Central Africa. In: 14th International AIDS Conference; 2002; Barcelona, Spain.
135. Takehisa J, Kraus MH, Ayouba A, Bailes E, Van Heuverswyn F, Decker JM, et al. Origin and biology of simian immunodeficiency virus in wild-living western gorillas. J Virol 2009; 83:1635–1648.
136. Marx PA, Alcabes PG, Drucker E. Serial human passage of simian immunodeficiency virus by unsterile injections and the emergence of epidemic human immunodeficiency virus in Africa. Philos Trans R Soc Lond B Biol Sci 2001; 356:911–920.
137. Drucker E, Alcabes PG, Marx PA. The injection century: massive unsterile injections and the emergence of human pathogens. Lancet 2001; 358:1989–1992.
138. Pepin J, Plamondon M, Alves AC, Beaudet M, Labbe AC. Parenteral transmission during excision and treatment of tuberculosis and trypanosomiasis may be responsible for the HIV-2 epidemic in Guinea-Bissau. AIDS 2006; 20:1303–1311.
139. Pepin J, Labbe AC, Mamadou-Yaya F, Mbelesso P, Mbadingai S, Deslandes S, et al. Iatrogenic transmission of human T cell lymphotropic virus type 1 and hepatitis C virus through parenteral treatment and chemoprophylaxis of sleeping sickness in colonial Equatorial Africa. Clin Infect Dis 2010; 51:777–784.
140. Freeman EE, Weiss HA, Glynn JR, Cross PL, Whitworth JA, Hayes RJ. Herpes simplex virus 2 infection increases HIV acquisition in men and women: systematic review and meta-analysis of longitudinal studies. AIDS 2006; 20:73–83.
141. de Sousa JD, Muller V, Lemey P, Vandamme AM. High GUD incidence in the early 20 century created a particularly permissive time window for the origin and initial spread of epidemic HIV strains. PLoS One 2010; 5:e9936.
142. Weiss HA, Quigley MA, Hayes RJ. Male circumcision and risk of HIV infection in sub-Saharan Africa: a systematic review and meta-analysis. AIDS 2000; 14:2361–2370.
143. Auvert B, Buve A, Lagarde E, Kahindo M, Chege J, Rutenberg N, et al. Male circumcision and HIV infection in four cities in sub-Saharan Africa. AIDS 2001; 15 (Suppl 4):S31–S40.
144. Orroth KK, White RG, Freeman EE, Bakker R, Buve A, Glynn JR, et al.Attempting to explain heterogeneous HIV epidemics in sub-Saharan Africa: potential role of historical changes in risk behaviour and male circumcision.Sex Transm Infect 2011; 87:640–645.
145. Zhu T, Korber BT, Nahmias AJ, Hooper E, Sharp PM, Ho DD. An African HIV-1 sequence from 1959 and implications for the origin of the epidemic. Nature 1998; 391:594–597.
146. Worobey M, Gemmel M, Teuwen DE, Haselkorn T, Kunstman K, Bunce M, et al. Direct evidence of extensive diversity of HIV-1 in Kinshasa by 1960. Nature 2008; 455:661–664.
147. Vidal N, Peeters M, Mulanga-Kabeya C, Nzilambi N, Robertson D, Ilunga W, et al. Unprecedented degree of human immunodeficiency virus type 1 (HIV-1) group M genetic diversity in the Democratic Republic of Congo suggests that the HIV-1 pandemic originated in central Africa. J Virol 2000; 74:10498–10507.
148. Pepin J. Societies in transition. In: The origins of AIDS. Cambridge: Cambridge University Press; 2011. pp. 59–83.
149. Hart JA. From subsistence to market: a case study of the Mbuti net hunters. Hum Ecol 1978; 6:325–353.
150. Fa J, Juste J, del Val J, Castroviejo J. Impact of market hunting on mammal species in equatorial Guinea. Conserv Biol 1995; 9:1107–1115.
151. Wilkie D, Carpenter J. Bushmeat hunting in the Congo Basin: an assessment of impacts and options for mitigation. Biodiver Conserv 1999; 8:137–147.
152. Auzel P, Wilkie DS. Wildlife use in northern Congo: hunting in a commercial logging concession. In: Robinson JG, Bennett EL, editors. Hunting for sustainability in tropical forests. New York, New York: Columbia University Press; 2000. pp. 413–426.
153. Bennett EL, Milner-Gulland EJ, Bakarr MI, Eves HE, Robinson JG, Wilkie DS. Hunting the world's wildlife to extinction. Oryx 2002; 36:1–2.
154. Fa JE, Peres CA, Meeuwig J. Bushmeat exploitation in tropical forests: an intercontinental comparison. Conserv Biol 2002; 16:232–237.
155. Forests and the Democratic Republic of Congo. Opportunities in a time of crisis. Available at [Accessed October 2011]
156. Wolfe ND, Daszak P, Kilpatrick AM, Burke DS. Bushmeat hunting, deforestation, and prediction of zoonoses emergence. Emerg Infect Dis 2005; 11:1822–1827.
157. De Merode E, Cowlishaw G. Species protection, the changing informal economy, and the politics of access to the bushmeat trade in the Democratic Republic of Congo. Conserv Biol 2006; 20:1262–1271.
158. Laurent C, Bourgeois A, Mpoudi M, Butel C, Peeters M, Mpoudi-Ngole E, et al. Commercial logging and HIV epidemic, rural equatorial Africa. Emerg Infect Dis 2004; 10:1953–1956.
159. Mulanga C, Bazepeo SE, Mwamba JK, Butel C, Tshimpaka JW, Kashi M, et al. Political and socioeconomic instability: how does it affect HIV? A case study in the Democratic Republic of Congo. AIDS 2004; 18:832–834.
160. Secretariat général MdlS. Minisanté RDC. National Plan of Health Development NPHD 2011-2015. 2011. pp. 18–60.

Africa; cross-species transmission; emerging disease; non-human primate; simian foamy virus; simian immunodeficiency virus; simian T-cell lymphotropic virus

© 2012 Lippincott Williams & Wilkins, Inc.