MARCH2 is upregulated in HIV-1 infection and inhibits HIV-1 production through envelope protein translocation or degradation

MARCH2 is one of the MARCH family E3 ligases, which contains eleven members that play pivotal roles in controlling the turn-over of membrane proteins, such as MHC class I, MHC class II, and cell surface receptors. In this study, we found the expression of MARCH2 to be upregulated upon HIV-1 infection. MARCH2 inhibits the production and infection of HIV-1 through ligase activity-dependent envelope protein degradation and/or intracellular retention, a mechanism shared by MARCH8 that also leads to the inhibition of HIV-1 infection. Nevertheless, unlike MARCH8 and other MARCH proteins whose transcription levels are unrelated to viral infection, the expression level of MARCH2 is markedly upregulated upon HIV-1 infection, conferring MARCH2 a unique role in monitoring and regulating the HIV-1 infection-associated process. •The expression level of MARCH2 is dramatically upregulated upon HIV infection.•MARCH2 overexpression reduces HIV-1 production.•Knockdown of MARCH2 increases viral production.•MARCH2 degrades VSV-G via lysosome and reduces Env from the plasma membrane.•The function of MARCH2 is ligase activity-dependent.