Progress and prospects in HIV/AIDS pathogenicity research using rhesus macaque models: from SHIV model development to...

This review systematically summarizes the development and applications of Simian-Human Immunodeficiency Virus (SHIV) models in rhesus macaques conducted by our research group from 2001 to 2023. Over this two-decade span, we have made significant contributions to HIV/AIDS research through the development and characterization of various SHIV models. Beginning with the isolation and characterization of molecular clones with different pathogenicities from SHIV-89.6P, we progressed to investigating the mechanisms of small intestinal CD4+ T cell depletion in SHIV infection. Subsequently, we developed R5-tropic SHIV models that better mimic natural HIV infection and conducted in-depth studies on neutralizing antibody induction and neutralization resistance. This review examines these research achievements chronologically, discusses their significance in understanding HIV/AIDS pathogenesis, and presents future research prospects in this field. Our findings have contributed substantially to elucidating the molecular mechanisms of HIV pathogenicity and establishing platforms for vaccine and therapeutic development.