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JAIDS Journal of Acquired Immune Deficiency Syndromes:
Letters to the Editor

Genetic Characterization of Full-Length HIV Type 1 Genomes From 3 Infected Paid Blood Donors in Henan, China

Liu, Li PhD*; Su, Bo PhD*; Zhuang, Ke PhD*; Tien, Po PhD*; Chen, Zhiwei PhD*†; Zhang, Linqi PhD*†‡

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*Modern Virology Research Center and AIDS Center, State Key Laboratory of Virology, College of Life Sciences, Wuhan University Hubei, PR China, †Aaron Diamond AIDS Research Center, The Rockefeller University, New York, NY, ‡AIDS Research Center, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, PR China

Supported by the Special Fund of Wuhan University for the Modern Virology Research Center.

To the Editor:

China is facing increased danger of a widespread HIV-1 epidemic in high-risk populations such as injecting drug users (IDUs) and paid blood donors (PBDs) and of further dissemination from these high-risk populations to the general public. The virus has spread to every province and autonomous region, and the government estimates about 840,000 infections, of which only 89,067 have been reported.1 However, prevalence and incidence studies are woefully inadequate and the United Nations Joint Program on HIV/AIDS projects that there may be as many as 10 million infected people by 2010.2 Among all high-risk activities linked to HIV-1 transmission, IDU appears to play the most important role in the epidemic thus far.1-3 Many of these HIV-infected IDUs reside in southwest provinces such as Yunnan, Guangxi, and Sichuan, which is close to the Golden Triangle, where 70% of the world's heroin is produced.1 HIV-1 infection through illegal blood collection practices and blood transfusions in the central province of Henan constitutes a second important high-risk activity in China1 and it has recently generated a tremendous amount of media attention. Illegal blood collection practices in Henan involved the collection and pooling of blood from several donors. Following centrifugation, plasma was removed and the remaining blood cells were reinjected into the donors, often contaminated with HIV-1 or hepatitis C virus. Such practices, in addition to the reuse of needles and unsterilized equipment, provided the virus an easy and rapid route of transmission to the local population.

We have previously demonstrated that IDUs and PBDs harbor 2 distinct HIV strains in China.4,5 The PBD and transfusion recipients in the central provinces of Henan and Hubei were found to harbor HIV-1 subtype B′ similar to that originally identified in Thailand, whereas the IDUs in Yunnan, Guangxi, and Xinjiang carried HIV-1 circulating recombinant forms 07 and 08 (CRF07 and 08) resembling those in India.4-6 However, our previous studies were focused only on p17 and C2-V3 regions of the virus and the conclusions drawn from the studies may not reflect the genetic information of the entire viral genome. To further characterize the genetic features of HIV-1 in PBDs, we have amplified and sequenced 3 full-length HIV-1 genomes from 3 infected patients residing in 3 different locations within Henan: Sanmenxia, Shangqiu, and Shangcai. These patients came to Beijing seeking a medical checkup and antiretroviral treatment in 2002. These 3 HIV-1 clones are named 02HNsmx2, 02HNsq4, and 02HNsc11, respectively, based on their year of sampling and geographic origins. The obtained sequences have been deposited into the GenBank (accession numbers are DQ007901-3). Because these 3 places are hundreds of miles apart, the sequence information obtained is unlikely to be biased toward one particular location. Despite geographic separation, phylogenetic analysis shows that these 3 viruses cluster tightly among themselves and are genetically closest to the HIV-1 B′ strain previously identified in Yunnan (CNRL42)7 and Henan (CNHN24 and CNLTG0218) (Fig. 1),8,9 suggesting the possibility of a common origin of a single founder virus for the HIV-1 epidemic in Henan. Recombination analysis using the SimPlot (Stuart Ray, http://www.med.jhu.edu/deptmed/sray/download) program has also confirmed phylogenetic findings and revealed no recombinant breakpoints with any reference sequences from the Los Alamos database and those circulating in China (data not shown).

Figure 1
Figure 1
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Our current results have reaffirmed our previous findings that HIV-1 in PBDs represents a relatively homogenous population despite geographic distances. In our previous studies, 121 samples were collected from 15 of the 18 administrative cities across Henan, yet sequences are highly linked and the degree of interpatient variation among infected individuals is almost in the range of that normally observed within an infected individual or between known transmission pairs.5 Such degree of sequence similarity strongly suggests that most, if not all, of the PBDs in Henan and perhaps in the neighboring provinces were infected by a rather homogenous viral population within a short window period. This concurs with the time frame when illegal blood donation practices occurred in Henan. A small number of PBDs started their blood donation as early as 1985, but the majority (>90%) were actively involved between 1992 and 1996.10 Most PBDs donated blood multiple times, and mobile blood collection units were frequently used to collect blood at the village level. The unsafe practice of reinfusing the extracted cells from the pooled blood of several donors provided a unique opportunity for HIV-1 to bypass immune selection pressure exerted on the virus at the mucosal surfaces. This could partially help to explain the relative homogeneity of HIV-1 in Henan after an extended period of epidemic.

Where the initial donor virus came from and how it was introduced to Henan remain unclear. The small average genetic distance among these 3 full-length clones and their close relationship to other strains identified in Yunnan (CNRL42) and Henan (CNHN24 and CNLTG0218) suggest a common origin of a single founder virus of the HIV-1 epidemic in Henan. CNRL42 is the oldest strain among the three7-9 and it is therefore more likely to be the closest relative to the original strain transmitted to Henan. CNRL42 was initially identified from an IDU in Dehong prefecture, Yunnan, in 1991,7 whereas CNHN24 and CNLTG0218 were isolated approximately 10 years later in Henan.8,9 However, the problems in determining the possible origin and timing of the transmission of CNRL42-like strains to Henan are largely confounded by the rapid turnover of viral subtypes in Yunnan over the past 15 years. Whereas the initial HIV-1 epidemic among IDUs in Yunnan in 1989 was caused by a mixture of viruses closely resembling the typical North American subtype B and the Thai B (B′), the subsequent epidemic was largely dominated by the subtype B′ from 1991 to 1996.7,11 During these years, a second epidemic began among IDUs with strains genetically related to subtype C viruses from India.12,13 A circulating recombinant form between subtypes A and E (CRF01) was also described in a commercial sex worker in Yunnan who had worked in Thailand for a prolonged period.14 Given that multiple subtype viruses were circulating in the same high-risk group, it is not surprising that recombinant forms are becoming predominant in some parts of Yunnan.15-18 In samples collected in 1996 and 1997, recombinant viruses between subtypes B′ and C (CRF07 and CRF08) were found along drug trafficking routes from Yunnan to Guangxi and Xinjiang provinces.6 By 1998, HIV-1 infection had been reported in all 31 provinces in China. As a result of highly dynamic changes in HIV-1 subtypes in Yunnan, it is virtually impossible to describe the chain of transmission events that led to epidemics in Henan. However, the close relationship between viruses found in Henan and some of the early subtype B′ sequences in Yunnan strongly suggests that the major outbreak of HIV-1 among PBDs is likely derived from a common origin genetically similar to CNRL42. We believe that information provided in this study will have important implications for future design and development of an effective vaccine, antiretroviral drugs, and of necessary assays and reagents for testing future candidate vaccines and antiretroviral drugs targeted at the HIV-1 strains circulating in central China.

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ACKNOWLEDGMENT

We are indebted to the patients for their participation.

Li Liu, PhD*

Bo Su, PhD*

Ke Zhuang, PhD*

Po Tien, PhD*

Zhiwei Chen, PhD*†

Linqi Zhang, PhD*†‡

*Modern Virology Research Center and AIDS Center State Key Laboratory of Virology College of Life Sciences Wuhan University Hubei PR, China

†Aaron Diamond AIDS Research Center The Rockefeller University New York, NY

‡AIDS Research Center Chinese Academy of Medical Sciences and Peking Union Medical College Beijing, PR, China

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REFERENCES

1. State Council AIDS Working Committee Office and UN Theme Group on HIV/AIDS in China. A Joint Assessment of HIV/AIDS Prevention, Treatment and Care in China; 2004.

2. The UN Theme Group on HIV/AIDS in China. HIV/AIDS: China's Titanic Peril; 2002.

3. China Ministry of Health and UN Theme Group on HIV/AIDS in China. A Joint Assessment of HIV/AIDS Prevention, Treatment and Care in China; 2003.

4. Su B, Liu L, Wang F, et al. HIV-1 subtype B′ dictates the AIDS epidemic among paid blood donors in the Henan and Hubei provinces of China. AIDS. 2003;17:2515-2520.

5. Zhang L, Chen Z, Cao Y, et al. Molecular characterization of human immunodeficiency virus type 1 and hepatitis C virus in paid blood donors and injection drug users in China. J Virol. 2004;78:13591-13599.

6. Rodenburg CM, Li Y, Trask SA, et al. Near full-length clones and reference sequences for subtype C isolates of HIV type 1 from three different continents. AIDS Res Hum Retroviruses. 2001;17:161-168.

7. Graf M, Shao Y, Zhao Q, et al. Cloning and characterization of a virtually full-length HIV type 1 genome from a subtype B′-Thai strain representing the most prevalent B-clade isolate in China. AIDS Res Hum Retroviruses. 1998;14:285-288.

8. Feng FM, Bao ZY, Zhuang DM, et al. Cloning and characterization of a full-length HIV-1 genome of a prevalent subtype B-Thai strain in Henan Province [in Chinese]. Zhonghua Shi Yan He Lin Chuang Bing Du Xue Za Zhi. 2004;18:356-359.

9. Wei M, Xing H, Hong K, et al. Biased G-to-A hypermutation in HIV-1 proviral DNA from a long-term non-progressor. AIDS. 2004;18:1863-1865.

10. Wu Z, Zhang J, Detels R, et al. Risk factors for initiation of drug use among young males in southwest China. Addiction. 1996;91:1675-1685.

11. Weniger BG, Takebe Y, Ou CY, et al. The molecular epidemiology of HIV in Asia. AIDS. 1994;8:S13-S28.

12. Li DQ, Zheng XW, Zhang GY. Study on the distribution HIV-1 C subtype in Ruili and other counties, Yunnan, China [in Chinese]. Zhonghua Liu Xing Bing Xue Za Zhi. 1996;17:337-339.

13. Luo C, Tian C, Hu D. HIV-1 subtype C in China. Lancet. 1995;345:1051-1052.

14. Cheng H, Zhang J, Capizzi J, et al. HIV-1 subtype E in Yunnan, China. Lancet. 1994;344:953-954.

15. Su L, Graf M, Zhang Y, et al. Characterization of a virtually full-length human immunodeficiency virus type 1 genome of a prevalent intersubtype (C/B′) recombinant strain in China. J Virol. 2000;74:11367-11376.

16. Yang R, Kusagawa S, Zhang C, et al. Identification and characterization of a new class of human immunodeficiency virus type 1 recombinants comprised of two circulating recombinant forms, CRF07_BC and CRF08_BC, in China. J Virol. 2003;77:685-695.

17. Yang R, Xia X, Kusagawa S, et al. On-going generation of multiple forms of HIV-1 intersubtype recombinants in the Yunnan Province of China. AIDS. 2002;16:1401-1407.

18. Piyasirisilp S, McCutchan FE, Carr JK, et al. A recent outbreak of human immunodeficiency virus type 1 infection in southern China was initiated by two highly homogeneous, geographically separated strains, circulating recombinant form AE and a novel BC recombinant. J Virol. 2000;74:11286-11295.

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