Bystander CD4 T-cell death is inhibited by broadly neutralizing anti-HIV antibodies only at levels blocking cell-to-cell viral transmissionThe progressive loss of CD4+ T cells during HIV infection of lymphoid tissues involves both the apoptotic death of activated and productively infected CD4 T cells and the pyroptotic death of large numbers of resting and abortively infected bystander CD4 T cells. HIV spreads both through cellular release of virions and cell-to-cell transmission involving the formation of virological synapses. Cell-to-cell transmission results in high-level transfer of large quantities of virions to the target cell exceeding that achieved with cell-free virions.
Membrane-associated RING-CH (MARCH) 1 and 2 are MARCH family members that inhibit HIV-1 infectionMembrane-associated RING-CH 8 (MARCH8) is one of 11 members of the MARCH family of RING finger E3 ubiquitin ligases and down-regulates several membrane proteins (e.g. major histocompatibility complex II [MHC-II], CD86, and transferrin receptor). We recently reported that MARCH8 also targets HIV-1 envelope glycoproteins and acts as an antiviral factor. However, it remains unclear whether other family members might have antiviral functions similar to those of MARCH8. Here we show that MARCH1 and MARCH2 are MARCH family members that reduce virion incorporation of envelope glycoproteins.