Molecular Epidemiology Of HIV-1 Among MSM And T/F HIV-1 Related Neurocognitive Disorder (HAND) In Humanized Mice

In the recent years,HIV-1 epidemic and dynamics of viral recombination among men who have sex with men are emerging in China.However,little is known about which gene-type are prevalent among MSM in China.So,we focused on the recent HIV-1epidemic and dynamics of viral recombination among men who have sex with men in China.Moreover,Human immunodeficiency virus（HIV）-associated neurocognitive disorder is one of the common causes of cognitive dysfunction and morbidity among infected patients.However,to date,it remains unknown if a transmitted/founder（T/F）HIV-1leads to HAND during the acute phase of infection.Since it is impossible to answer this question in humans.So we studied NOD.Cg-Prkdc side Il2rgtm1Wjl/SzJ mice（NSG）reconstituted with human PBMC（NSG-HuPBL）,followed by the peritoneal challenge with the chronic HIV-1_JR-FL and the T/F HIV-1_BJZS7.The main content of this article is as follows.Firstly,Phylogenetic analysis of HIV-1 was conducted to understand viral genotypes over time based on gag and pol genes.Single-genome amplification was used to obtain nearly full-length HIV-1 genome for recombinant analysis and to trace the origin of newly identified viral strains.HIV-1 gag and pol gene sequences were successfully amplified by PCR from 76 infected MSM patients identified in 2011（n=17）,2012（n=23）and 2013（n=36）,respectively.Basing on the gag,phylogenetic analysis revealed three major genotypes,including CRF01_AE（38,55.1%）,CRF07_BC（21,30.4%）and B/B’（4,5.8%）.The rest were new recombinant strains（6,8.7%）.Of them,CRF07_BC strains displayed a significant increase from 4（19%）in 2012 to 13（41.9%）in 2013（p<0.01）,resulting in parallel epidemics with CRF01_AE among MSM.Moreover,new recombinant strains were mainly between CRF01_AE and CRF07_BC strains.Secondly,By measuring viral load,P24 antigenemia and P24⁺cells in peripheral blood and various tissue compartments,we found that systemic infections were rapidly established in NSGHuPBL mice by both HIV-1 strains.Although comparable peripheral viral loads were detected during acute infection,the T/F virus appeared to cause less CD4⁺T cell loss and less numbers of infected cells in different organs and tissue compartments.Both viruses,however,invaded brains with P24⁺/CD3⁺T cells detected primarily in the meninges,cerebral cortex and perivascular areas.Critically,brain infections with HIV-1 _JR-FL but not with HIV-1_BJZS7 resulted in damaged neurons together with activated microgliosis and astrocytosis as determined by significantly increased numbers of Iba1⁺microglial cells and GFAP⁺astrocytes,respectively.The increased Iba1⁺microglia was correlated positively with levels of P24 antigenemia and negatively with numbers of NeuN⁺neurons in brains of infected animals.In all,The emerging HIV-1 epidemic among MSM in China has resulted from dominating CRF01_AE infections to the nearly parallel evolution of CRF01_AE and CRF07_BC viruses.This change has further led to the emergence of new recombinant strains.What’s more,the NSG-HuPBL model using a T/F virus shown the significant implications to HIV-1 pathogenesis and neuropathology.These results have implication for HIV-1 prevention and early treatment of HAND.