Characterization Of Viral Reservoirs In Latent Infected Rhesus Macaques For AIDS

Part 1:Therapeutic Efficacy of Potent HIV Fusion Inhibitor in Rhesus Macaques and Characterization of Viral ReservoirsAntiretroviral therapy(ART)with multiple drugs in a combination can effectively suppress HIV replication,but it does not eliminate the viral reservoirs,and lifelong treatment will ultimately result in cumulative toxicities and drug resistance.Currently,viral reservoir represents the most important challenge for HIV cure but the molecular mechanisms and characteristics underlying its formation and existence as well as the viral rebound remain unclear.In this study,we describe the therapeutic efficacy of new HIV fusion-inhibitory lipopeptides in SHIVSF162P3-infected rhesus macaques,which exhibited extremely potent antiviral activities in vivo.Monotherapy with a low dose lipopeptide LP-98 sharply reduced SHIVSF162P3 replication to undetectable levels in rhesus macaques and achieved a posttreatment control(PTC)efficacy in a subset of treated monkeys.Interestingly,we found that the monkeys with stable viral rebound(SVR)had relatively higher viral DNA copies in superficial lymph nodes(neck and axilla),the PTC monkeys hided lower viral DNA in deep lymph nodes(mesentery and parenteral),whereas the monkeys with unstable viral rebound(UVR)exhibited medium levels of viral DNA in both the superficial and deep lymph nodes.Quantitative viral outgrowth assay(QVOA)revealed robust outgrowth in various lymph nodes of the SVR and UVR monkeys but not the PTC monkeys.Moreover,we verified that the PTC monkeys had lower levels of PD-1+central memory CD4+T cells in the spleen and axillary/mesenteric lymph nodes than the SVR and UVR monkeys,and that CD8+T cells contributed critically to the control of the SHIVSF162P3 replication.Therefore,our studies have not only measured the therapeutic efficacy of a novel HIV entry inhibitor for potential HIV cure but also provided insights into the latent viral reservoir.Part 2:Characteristics of CD32 in SIVmac239-infected rhesus macaques with antiretroviral therapy.It is a highly controversial argument in recent years about whether CD32 is a marker for latent reservoirs.By using SIVmac239-infected rhesus macaques with antiretroviral therapy,we study the characteristics of CD32 expressed on resting,activated and/or memory CD4+T-cell subsets,and analyze its potential as a biomarker of HIV/SIV reservoirs.Four monkeys chronically infected with SIVmac239 were intramuscularly administrated with antiretroviral therapy.Using this animal model,we detect the plasma viral loads,CD4+T-cell counts,CD4/CD8 ratios,and the percentages of CD32 expressed in different CD4+T-cell subsets at the different stages.Compared with the pre-infection stage,the percentages of CD32 expressed in activated naive CD4+T cells and HLA-DR+CD4+T-cell subsets were significantly increased at the post-infection stage,and there were no changes of the percentages of CD32 expressed in resting CD4+T cells,resting naive CD4+T cells,resting central memory CD4+T cells,resting effector memory CD4+T cells,and resting TEMRA CD4+T cells.This study provides more data for the view that CD32 is not the main biomarker of SIV reservoirs,and provides insight for future AIDS treatment.