Downregulates CD4 and MHC I from the cell surface to prevent superinfection and enhance virion release, as well as avoid detection by cytotoxic T cells, respectively; increases virion infectivity by excluding host restriction factor SERINC3/5 from the virus particles; promotes antiapoptotic (Fas/TNF) and survival (Erk MAPK) signals to enhance persistence of infected cells, etc. Not essential for viral replication in vitro, but Nef-defective HIV-1 virions result in slow/no progression to AIDS. This evidence concerns the gene CD4 and AIDS.