Human immunodeficiency virus type 1 particles pseudotyped with envelope proteins that fuse at low pH no longer require Nef for optimal infectivity

We have investigated the effects of Nef on infectivity in the context of va rious viral envelope proteins. These experiments were performed with a mini mal vector system where Nef is the only accessory protein present. Our resu lts support the hypothesis that the route of entry influences the ability o f Nef to enhance human immunodeficiency virus (HIV) infectivity. We show th at HIV particles pseudotyped with Ebola virus glycoprotein or vesicular sto matitis virus glycoprotein (VSV-G), which fuse at low pH, do not require Ne f for optimal infectivity. In contrast, Nef significantly enhances the infe ctivity of virus particles that contain envelope proteins that fuse at neut ral pH (CCR5-dependent HIV Env, CXCR4-dependent HIV Env, or amphotropic mur ine leukemia virus Env). In addition, our results demonstrate that virus pa rticles containing mixed CXCR4-dependent HIV and VSV-G envelope proteins sh ow a conditional requirement for Nef for optimal infectivity, depending on which protein is allowed to facilitate entry.