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Abstract: The northern pig-tailed macaque (Macaca leonina) has been identified as an independent species of Old World monkey, and we previously found that PBMCs from M. leonina were susceptible to human immunodeficiency virus type 1 (HIV-1), which may be due to the absence of a TRIM5 protein restricting HIV-1 replication. Here we investigated the infection potentials of six laboratory adapted HIV-1 strains and three primary HIV-1 isolates in PBMCs from M. leonina. The results indicate that these strains are characterized by various but low replication levels, and among which, HIV-1^sub NL4-3^ shows the highest replication ability. Based on the abundant evidence of species-specific interactions between restriction factors APOBEC3 and HIV/SIV-derived Vif protein, we subsequently examined the replication potentials of vif-substituted HIV-1 (HSIV) in M. leonina PBMCs. Notably, HSIV-vif^sub mac^ and stHIV-1^sub SV^ chimeras, two HIV-1^sub NL4-3^-derived viruses encoding the viral infectivity factor (Vif) protein from SIV^sub mac239^, replicated robustly in cells from M. leonina, which suggests that HSIV could effectively antagonize the antiviral activity of APOBEC3 proteins expressed in cells of M. leonina. Therefore, our data demonstrate that M. leonina has the potential to be developed into a promising animal model for human AIDS.
Keywords: HIV-1; HSIV; Replication; PBMC; Northern pig-tailed macaque (Macaca leonina)
The lack of animal models that can be efficiently infected by HIV-1 has been a major impediment to the study of AIDS, anti-HIV-1 drugs and vaccines (Hatziioannou & Evans, 2012; Zhang et al, 2007). Presently, the most widely used non-human primate models for HIV/AIDS research are rhesus (Macaca mulatta), pig-tailed and cynomolgus macaques (M. fascicularis) infected with simian immunodeficiency viruses (SIVs) or SIV/HIV chimeric viruses (SHIVs) encompassing the HIV-1 env, tat, rev and vpu genes or reverse transcriptase gene (Baroncelli et al, 2008; Hatziioannou & Evans, 2012). Although these models have offered us with abundant information on immunopathogenesis and antiretroviral strategies (Evans & Silvestri, 2013; Lackner & Veazey, 2007), they have limitations largely due to the significant genetic differences between HIV-1 and SIV (Ambrose et al, 2007). SHIVs contain certain HIV-1 genes, but the absence of other HIV-1 genes has restricted their functional evaluation in viral pathogenesis or as targets for antiretroviral therapies in vivo.
Among Old World monkeys, the pig-tailed macaque is the only primate that can be infected...