Is human herpesvirus-7 a marker or a competitor for HIV progression?
Boutolleau, Davida,c; Bonduelle, Oliviab; Agut, Henria; Gautheret-Dejean, Agnèsa,d,; and the French ALT Study Group
aLaboratoire de Virologie, UPRES EA 2387, and bLaboratoire d'Immunologie Cellulaire et Tissulaire, Groupe Hospitalier Pitié-Salpêtrière, Paris, France; cLaboratoire de Microbiologie, Unité de Virologie, Hôpital de Bicêtre, Le Kremlin-Bicêtre, France; and dLaboratoire de Microbiologie, Faculté des Sciences Pharmaceutiques et Biologiques, Paris, France.
Received: 16 May 2003; accepted: 3 June 2003.
Human herpesvirus-7 (HHV-7) is a CD4 T-lymphotropic betaherpesvirus, highly prevalent in the adult population. The pathogenic role of this virus still remains unclear. From data obtained in vitro, HHV-7 might be expected to slow the progression of HIV infection. Indeed, both viruses use the glycoprotein CD4 as a cell receptor, and a reciprocal competition has been demonstrated for entry in CD4 cells . Conversely, as for other herpesviruses, HHV-7 replication might be facilitated through the deficiency of immune control associated with HIV infection. In order to approach the question of interactions between both viruses in vivo, HHV-7 DNA was detected and quantified in the peripheral blood mononuclear cells (PBMC) from a control group of 31 HIV-seronegative individuals and two distinct groups of HIV-seropositive patients who had never received any antiretroviral therapy: 68 patients from the French ALT Cohort of long-term non-progressors (LTNP) , and 30 patients classified as progressors. HHV-7 DNAemia was studied using a real-time polymerase chain reaction assay based on TaqMan technology (we used the ABI PRISM 7700 sequence detection system; Applied Biosystems, Courtaboeuf, France) .
The rate of HHV-7 DNA detection was statistically lower in HIV-seropositive (38%) than in HIV-seronegative individuals (87%) (P < 0.0001). However, this HHV-7 detection rate in HIV-seropositive patients was much higher than the 3% value obtained by means of quantitative-competitive polymerase chain reaction applied to whole blood in a previous study , which probably reflects differences in both assay sensitivity and DNA input. This rate was also higher in LTNP (48%) than in progressors (20%) (P = 0.018). This difference fit the variation of median CD4 T-lymphocyte count, which was significantly higher in LTNP (678 cells/μl) than in progressors (314 cells/μl) (P < 0.0001). Moreover, considering both groups os of HIV-seropositive patients together, the median CD4 T-lymphocyte count was higher in patients with detectable HHV-7 DNA than in patients without (640 and 488 cells/μl, respectively) (P = 0.008). No correlation was observed between the rate of HHV-7-DNA detection and the HIV load.
In agreement with the results of viral detection, the median HHV-7 load was lower in HIV-seropositive patients [111 equivalent genome copy numbers (EqCop)/106 PBMC; 11–1333] than in HIV-seronegative individuals (987 EqCop/106 PBMC; 16–14 545) (P = 0.0004). Among HIV-seropositive patients, no statistical correlation was demonstrated between the HHV-7 load and either the HIV load or CD4 T-lymphocyte count, when considering all subjects as a whole or LTNP and progressors separately. Taking advantage of the fact that LTNP had been followed-up for a median time of 3 years, the analysis of HHV-7 DNAemia was repeated at one and 2 years after the initial evaluation; both detection rates (53 and 47%, respectively) and DNA loads (106 and 142 EqCop/106 PBMC, respectively) were found to be stable over that period.
The finding that HHV-7 DNAemia was detected more frequently in HIV-seronegative than in HIV-seropositive individuals, and in LTNP more frequently than in progressors, might support the idea that HHV-7 did compete with HIV in vivo. Alternatively, this might reflect the decrease in CD4 T-lymphocytes, a key cell reservoir for HHV-7, throughout the course of HIV infection. Intriguingly, either hypothesis hardly fits with the current absence of statistical correlation between the HHV-7 load, and either the HIV load or CD4 T-lymphocyte count. Further studies, involving both a larger number of subjects and patients receiving HIV replication inhibitors, are warranted to determine to what extent HHV-7 can be considered as a negative marker or a competitor for HIV progression.
1. Lusso P, Secchiero P, Crowley RW, Garzino-Demo A, Berneman ZN, Gallo RC. CD4 is a critical component of the receptor for human hn herpesvirus 7: interference with human immunodeficiency virus. Proc Natl Acad Sci USA
2. Candotti D, Costagliola D, Joberty C, Bonduelle O, Rouzioux C, Autran B, et al
. Status of long-term asymptomatic HIV-1 infection correlates with viral load but not with virus replication properties and cell tropism. J Med Virol
3. Fernandez C, Boutolleau D, Manichanh C, Mangeney N, Agut H, Gautheret-Dejean A. Quantitation of HHV-7 genome by real-time polymerase chain reaction assay using MGB probe technology. J Virol Methods
4. Fabio G, Knight SN, Kidd M, Noibi SM, Johnson MA, Emery VC, et al
. Prospective study of human herpesvirus 6, human herpesvirus 7, and cytomegalovirus infections in human immunodeficiency virus-positive patients. J Clin Microbiol
© 2004 Lippincott Williams & Wilkins, Inc.
What does "Remember me" mean?
By checking this box, you'll stay logged in until you logout. You'll get easier access to your articles, collections,
media, and all your other content, even if you close your browser or shut down your
To protect your most sensitive data and activities (like changing your password),
we'll ask you to re-enter your password when you access these services.
What if I'm on a computer that I share with others?
If you're using a public computer or you share this computer with others, we recommend
that you uncheck the "Remember me" box.
Data is temporarily unavailable. Please try again soon.