Heterogeneous Evolution Of HIV-1 In Men Who Have Sex With Men(MSM) And Other Populations In China

The HIV epidemic in men who have sex with men(MSM)continues to grow in most countries.More than half of new HIV infections occur among MSM in both the United States of America and the United Kingdom.In China,the proportion of MSM among those newly diagnosed with HIV increased to 29.4%in 2011.MSM has become the new high risk population of HIV infection instead of intravenous drug user(IDU).A nationwide molecular epidemiological survey in MSM showed that CRF01_AE and CRF07_BC were the main HIV-1 strains circulating in MSM.There is an unmet need for studies focusing on the phylodynamics and virology of HIV transmission and acquisition risks for MSM and transmission dynamics within the MSM networks.Molecular phylogenetics is one of important tools to study the properties of HIV sequences.Molecular phylogenetics can analysis hereditary molecular differences,mainly in DNA sequences,to gain information on an organism's evolutionary relationships.In recent years,the tool has been widely used in HIV research.In this study,we used this tool to identify the subtypes and unique recombination of HIV viruses,the selection of CRF01_AE,and the variation of CRF07_BC population diversity.We also combined the molecular phylogenetics and the molecular epidemiology information to infer the geographic distribution and transmission of CRF01_AE.In the first part of out study,seventy-six HIV-1 infected samples were collected and used for the genetic analysis.The following risk groups were identified:MSM(14/76,18.4%);heterosexuals(38/76,50%);IDUs(13/76,17.1%);unknown(11/76,14.4%).The classifications of the 76 samples were following,CRF01_AE(21/76,27.6%),CRF07_BC(22/76,28.9%),CRF08_BC(10/76,13.1%),B(14/76,18.4%)and URF(9/76,11.8%).We also get the near full length genomes(NFLG)of two novel CRF01_AE/CRF07_BC recombination.In the second part of this study,all of the available pol fragments for CRF01_AE were obtained from the Los Alamos HIV database.The virus migrated from the Central African Republic to Thailand in Apr 1981(95%highest posterior density[May 1978,Sep 1983]).During the next a few years,Thailand became the primary epicenter as CRF01_AE spread across Southeast Asia.After 1997,we observed that the viruses had expanded their geographical distribution to many provinces in China.Guangxi and Liaoning were secondary epicenters,with a large extent of migration.In the third part of out study,all of the available NFLG sequences for CRF01_AE were obtained from the Los Alamos HIV database.Sequences isolated from MSM in China clustered in Clusters 1(92.5%)and 2(85.71%).The major risk factor for Cluster 3 was heterosexual transmission(62.16%).In env gene,Cluster 1(4.56×10-3subs/site/year)and 2(6.01×10-3subs/site/year)had higher evolutionary rates than Cluster 3(1.14×10-3subs/site/year).Two sites(HXB2:136 and 316)evolved similarly in Clusters 1 and 2,but not Cluster 3.In the forth part of out study,all of the available pol fragments for CRF07 BC were obtained from the Los Alamos HIV database.Two lineages(named I and II)were observed in CRF07 BC sequences isolated from Chinese patients.MSM was the predominant risk factor for patients in lineage I(82.8%).In contrast,IDU was the major risk factor for patients in lineage ?(43.6%).Three independent tests of subpopulation differentiation were significant(P<0.05).The d,dN and dS for Lineage I(0.0174 ±0.0013,0.044 ± 0.0028 and 0.0077 ± 0.0011 substitution/site,respectively)were significantly lower than those for Lineage ?(0.0289±0.002,0.072±0.005 and 0.014±0.0018 substitution/site,respectively).No significant difference was observed in selective pressure of two lineages.Conclusions:(1)The main strains circulating in this hospital in Zhejiang are CRF07 BC and CRF01_AE.The main transmission was sexual.We also found two novel CRF01_AE/CRF07_BC recombinations.(2)Thailand acted as the primary epicenter for multiple CRF01_AE strains that migrated worldwide.Guangxi and Liaoning acted as an important secondary source for the dissemination of CRF01_AE in China.(3)The HIV-1 CRF01_AE in MSM clustered in different cluster evolved differently than in other populations.(4)The HIV-1 CRF07_BC in MSM formed different lineage from other populations.These conclusions confirm that the evolution of HIV-1 in men who have sex with men(MSM)is different from other populations in China.This provides a new direction for the treatment of HIV and the development of vaccines,and also points out the direction for the prevention and control of HIV.