APOBEC3 family proteins mediate HIV-1 restriction in myeloid cells

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Initial goal is to clarify the APOBEC3 (A3)-mediated restriction of HIV-1 in THP-1 cells, as a model for HIV-1-infected myeloid cells. We created A3F and A3F/A3G-null THP-1 clones using CRISPR approach. HIV-1 Vif degrades A3 proteins in order to replicate efficiently in HIV-1-infected CD4 T cells.In THP-1 cells, disrupted A3F and A3F/A3G proteins fully restored infectivity of Vif-deficient HIV-1. Also, disruption of all A3 proteins (A3-null THP-1) also resulted in restoration of infectivity of Vif-deficient HIV-1. However, we found that endogenous A3H is not involved in HIV-1 restriction in THP-1 cells.Furthermore, we concluded that restriction of HIV-1 infection by A3 proteins is mediated through a deaminase-dependent (G-to-A mutations) and deaminase-independent mechanisms (accumulation of reverse transcription products). Collectively, our results indicate that A3 proteins are primary target of HIV-1 Vif to be degraded, in order to secure efficient HIV-1 replication in THP-1 cells.