Abstract
Background The Nef protein is a pathogenicity factor of HIV-1 that substantially increases virus replication in vivo by modulation of multiple host cell transport and signal transduction processes. Nef resides at the inner leaflet of the plasma membrane (PM), on membranes of endocytic and biosynthetic transport vesicles as well as in the cytoplasm as non-membrane associated form. Biological activities of Nef are generally thought to depend on its membrane association, which is mediated by the N-terminal SH4 (Src homology) domain, consisting of myristoylation and a stretch of basic residues. However, how targeting of Nef to select subcellular host cell membranes is achieved and which subcellular pools of Nef are involved in individual activities of the viral protein is not clear.
Highlights
The Nef protein is a pathogenicity factor of HIV-1 that substantially increases virus replication in vivo by modulation of multiple host cell transport and signal transduction processes
Nef resides at the inner leaflet of the plasma membrane (PM), on membranes of endocytic and biosynthetic transport vesicles as well as in the cytoplasm as non-membrane associated form
The full functionality of all SH4 domain containing constructs indicates that membrane association per se but not the specific steady state subcellular localization, membrane affinity, or anterograde transport pathway of Nef is essential for its biological activity
Summary
The Nef protein is a pathogenicity factor of HIV-1 that substantially increases virus replication in vivo by modulation of multiple host cell transport and signal transduction processes. Nef resides at the inner leaflet of the plasma membrane (PM), on membranes of endocytic and biosynthetic transport vesicles as well as in the cytoplasm as non-membrane associated form. Biological activities of Nef are generally thought to depend on its membrane association, which is mediated by the N-terminal SH4 (Src homology) domain, consisting of myristoylation and a stretch of basic residues. How targeting of Nef to select subcellular host cell membranes is achieved and which subcellular pools of Nef are involved in individual activities of the viral protein is not clear
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