MARCHF8 and HIV-1 infection: In this study, we explored various aspects of MARCH8 biology, shedding light on its antiviral mechanisms: (1) Mammalian MARCH8 proteins exhibit evolutionarily conserved antiviral activity, with key domains and motifs playing crucial roles; (2) Both the N-terminal and C-terminal CTs of MARCH8 are essential for its antiviral function; (3) MARCH8 effectively hinders cell-free HIV-1 infection but fails to impede cell-to-cell transmission.