HIV-1 replication and pathogenicity: lessons from macaque-tropic HIV-1 derivatives

Human immunodeficiency virus type 1 (HIV-1) is tropic for humans and replicates in virtually none of the other animal species. While various animal models to mimic the conflict between HIV-1 and human hosts have been proposed, nonhuman primates (NHPs) are thought to be most suitable from a purely scientific point of view for the HIV-1/AIDS model studies. Because NHPs are resistant to HIV-1, remodeling the HIV-1 genome is required to validate the productive infection of NHPs. Two types have been reported as retrofitted viruses, that is, SHIVs and HIV-1 derivatives. SHIVs are SIVs (simian immunodeficiency viruses) that carry a small portion of the HIV-1 genome, whereas HIV-1 derivatives are HIV-1 with a minimal sequence/genome modification. SHIVs have been successfully used for studies specifically targeting HIV-1 Pol-RT (reverse transcriptase) and Env proteins. HIV-1 derivatives can induce AIDS in NHPs under certain conditions. More importantly, HIV-1 derivatives contribute to elucidating the HIV-1 adaptation and virus-host interaction through analyzing the process of acquiring replication capacity and pathogenicity in restrictive hosts distinct from natural hosts. In this chapter, we summarize NHP model studies on HIV-1/AIDS using SIV, SHIV, or HIV-1 derivatives and discuss the significance of HIV-1 derivatives toward understanding the HIV-1 biology.