HIV-1 And HCV Transmission Bottleneck And Strain Origin Of Injecting Drug User

Since the first case of AIDS reported in 1981, humans have been struggling with HIV for more than 30 years. To date more than 70 million people worldwide have been infected with HIV-1. The HCV genome sequence was identified in 1989, but it had infected humans for more than one hundred years, now the number of infections worldwide is estimated to be 170 million. Although drug research and development have a major breakthrough, it still make no significant progress in vaccine research. The major technical obstacle is the high variation of the virus genome, which evolves a number of mechanisms to escape the immune pressure. However,at the acute stage of HIV and HCV infection, there is a bottleneck stage with very little genetic variation, this is a critical moment for intervention and transmission blocking. Therefore, it is important to find the target of vaccine prevention by studying the HIV-1 and HCV transmission bottleneck.Parenteral transmission is an important route for HIV-1 and HCV transmission, injecting drug users (IDUs) is the main group of parenteral transmission. Thus, IDUs have been a high risk of HIV-1 and HCV infection. The HIV-1 prevalence among IDUs is generally 10-30%, HCV prevalence is as high as 50%, and coinfection of the two viruses are also very common. Here we aim at studying HIV-1 and HCV transmission bottleneck in Chinese IDUs, obtaining sequences and related parameters of transmitted/founder virus (T/F virus), providing data and theoretical guidance for intervention and vaccine development.The HIV prevention trials network (HPTN) 033 and 058 cohort,observation cohort and intervention cohort of HIV-1 infection among IDUs,were conducted in 2002 and 2009. Here we collected acute infected subjects by proposing nucleic acid screening, and T/F virus sequences by using single genome sequencing (SGA) . Applying Highlighter plot,Poisson-Fitter and Bayesian sampling trees, we proposed quantitative and qualitative analyses of the HIV-1 and HCV T/F viruses in early infected IDUs, explored the risk behavior specific amino acid sites in HIV-1 transmission, and revisited the origin of HIV-1 and HCV epidemic in Xinjiang IDUs.The results are as follows: 1) We generated 1070 env region sequences from 33 HIV-1 early infected subjects and 773 5' half region sequences from 27 HCV early infected subjects by using SGA; 2) established a quantitative analysis method of T/F virus; 3 ) The rates of multiple virus transmission (39% versus 52%) and the maximum intra-patient sequence diversity (0.052 versus 0.093) for HIV-1 and HCV reflect a relatively discrepancy of transmission bottleneck; 4) The most recent common ancestor (MRCA) of CRF07 BC in Xinjiang IDUs was date back to 1992;5 ) Predominate viral HCV genotypes circulating in Xinjiang are 3a, 3b and lb. Xinjiang lb strain were discovered originated from American and European rather than South China. The MRCA of Xinjiang 1b was dated to 1990(95% CR, 1984-1994), more than fifteen years later than that of South China. Genotype 3a was introduced into Xinjiang in 1973, five years after to Yunnan in 1968, they have the same origin. HCV 3b epidemic in China arose from a single introduction 20 years ago, then spread to Xinjiang and other region by fast exponential growth. 6) CRF07_BC T/F virus of IDU and MSM show a few risk behavior specific amino acid sites.In our study, the multiple transmission rates of HIV-1 and HCV (39%versus 52%, p=0.29, Fisher's exact test) and the observed maximum intra-patient sequence diversity (0.052 versus 0.093) reflect a relatively discrepancy of transmission bottleneck. It may be the reason of incidence drop for HIV-1 (8.8% to <2%) and HCV (52% to 32%) between HPTN033 and HPTN058. The epidemic of HCV in Xinjiang are more complicate than HIV-1, with more than one predominate genotypes (3a, 3b and lb)and longer epidemical history. The introduction of HIV-1 CRF07_BC and HCV 3b to Xinjiang IDUs are all associated with drug trade.In summary, this study compared the transmission bottleneck of HIV-1 and HCV in parenteral transmission by subjects collected from two international cohorts, enriches the international database. This study also established a simple and intuitive method for T/F virus evaluation. These results promote the study of HIV-1 and HCV transmission dynamics and natural history, and provide scientific guidance for targeted intervention and vaccination.