 Nef localizes primarily to the cytoplasm but also partially to the Plasma membrane (PM) and is one of many pathogen-expressed proteins, known as virulence factors, which function to manipulate the host's cellular machinery and thus allow infection, survival or replication of the pathogen.Nef stands for "Negative Factor" and although it is often considered dispensable for HIV-1 replication, in infected hosts the viral protein markedly elevates viral titers.The expression of Nef early in the viral life cycle ensures T-cell activation and the establishment of a persistent state of infection, two basic attributes of HIV infection.