| 1. HIV-1 epidemic in Yunnan province of ChinaDating back to the first epidemic among injection drug users in 1989, the Yunnan province has had the highest number of human immunodeficiency virus type 1 (HIV-1) infections in China. However, the molecular epidemiology of HIV-1 in Yunnan has not been fully characterized. Using immunoassays, we identified 103,015 accumulated cases of HIV-1 infections in Yunnan between 1989 and 2004. We studied 863 patients representing Yunnan's 16 prefectures from four risk groups,11 ethnic populations, and ten occupations. We identified three major circulating subtypes:C/CRF07_BC/CRF08_BC (53%), CRF01_AE (40.5%), and B (6.5%) by analyzing the sequence of p17, which is part of the gag gene. For patients with known risk factors,90.9% of injection drug users had C/CRF07_BC/CRF08_BC viruses, whereas 85.4% of CRF01_AE infections were acquired through sexual transmission. No distinct segregation of CRF01_AE viruses was found among the Dai ethnic group. Geographically, C/CRF07_BC/CRF08 BC was found throughout the province, while CRF01_AE was largely confined to the prefectures bordering Myanmar. Furthermore, C/CRF07_BC/CRF08_BC viruses were found to consist of a group of viruses, including C, CRF08_BC, CRF07_BC, and new BC recombinants, based on the characterization of their reverse transcriptase genes. This is the first report of a province-wide HIV-1 molecular epidemiological study in Yunnan. While C/CRF07_BC/CRF08_BC and CRF01_AE are codominant, the discovery of many sexually transmitted CRF01_AE cases is new and suggests that this subtype may lead to a new epidemic in the general Chinese population. We discuss implications of our results for understanding the evolution of the HIV-1 pandemic and for vaccine development.2. The establishment of B'SHIV/Chinese rhesus macaques modelThe increasing prevalence of HIV-1 subtype B', one of the major genotypes in China and Southeast Asia, calls for efforts to develop a relevant animal model to study viral transmission and pathogenesis. Since there are significant sequence differences between B'HIV-1 and other SHIVs in env gene, a new SHIV, designated SHIVB'WHU, was generated. The in vitro characteristics have been discussed by Dr. Ke Zhuang in her Ph.D dissertation. However, the in vivo characteristics have not been studied. Serial passages of SHIVB'WHU were conducted in Chinese macaques to enhance viral infectivity. Moreover, viral variants in different tissues were studied to understand the site of viral replication and adaptation during the acute phase of infection, which has not been previously studied. The infectivity of SHIVB'WHU was enhanced in macaques during the serial passage as determined by viral load measurement. Interestingly, the enhanced infectivity did not result in altered CCR5-tropism and was unlikely associated with sequence variation in env genes recovered from lymphocytes of peripheral blood, small intestines and various tissues. The minimal variation in env is probably due to the lack of strong selection pressure during the acute phase of SHIVB'WHU infection in Chinese macaques. Significant CD4+ T cell loss was not found in small intestines of P3-P4 infected animals. Our data indicate that SHIVB'WHU is replication-competent and has adapted in Chinese rhesus macaques. The model of SHIVB'WHU/Chinese rhesus macaque can be used as a more appropriate model for vaccine research and microbicide evaluation. |
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