SIV-specific rhesus CD4 T cells expressing African green monkey TRIM5α exhibit prolonged persistence and enhanced antiviral function. (VIR1P.1153)

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Abstract Infection of CD4 T cells by HIV/SIV inhibits the formation of robust antiviral responses. Furthermore, HIV-specific CD4 T cells are preferentially infected and eliminated in vivo. This highlights the importance of protecting virus-specific CD4 T cells to effectively study their antiviral mechanisms. In this study, we have shown that African green monkey (Agm) TRIM5α restricts SIVmac239 replication in primary rhesus macaque CD4 T cells and synergizes with an intrinsic resistance present in some CD4 T-cell clones. Importantly, AgmTRIM5α-transduced effector CD4 T cells exhibit an increased ability to suppress viral replication in infected target cells. This increase in antiviral effector function was strongly linked to decreased infection and prolonged persistence of the AgmTRIM5α-expressing effectors. Hence, AgmTRIM5α restriction in rhesus CD4 T cells offers an approach to evaluate their anti-SIV effector functions. Currently, we are pursuing studies to determine the effectiveness of SIV-specific CD8 and CD4 T cells in controlling infection in an adoptive transfer model, where the genetically modified CD4 T-cell clones express AgmTRIM5α to prolong their persistence in vivo.