Abstract
BackgroundHIV-1 formation is driven by the viral structural polyprotein Gag, which assembles at the plasma membrane into a hexagonal lattice. The C-terminal p6Gag domain harbors short peptide motifs, called late domains, which recruit the cellular endosomal sorting complex required for transport and promote HIV-1 abscission from the plasma membrane. Similar to late domain containing proteins of other viruses, HIV-1 p6 is phosphorylated at multiple residues, including a highly conserved serine at position 40. Previously published studies showed that an S40F exchange in p6Gag severely affected virus infectivity, while we had reported that mutation of all phosphorylatable residues in p6Gag had only minor effects.FindingsWe introduced mutations into p6Gag without affecting the overlapping pol reading frame by using an HIV-1 derivative where gag and pol are genetically uncoupled. HIV-1 derivatives with a conservative S40N or a non-conservative S40F exchange were produced. The S40F substitution severely affected virus maturation and infectivity as reported before, while the S40N exchange caused no functional defects and the variant was fully infectious in T-cell lines and primary T-cells.ConclusionsAn HIV-1 variant carrying a conservative S40N exchange in p6Gag is fully functional in tissue culture demonstrating that neither S40 nor its phosphorylation are required for HIV-1 release and maturation. The phenotype of the S40F mutation appears to be caused by the bulky hydrophobic residue introduced into a flexible region.
Highlights
HIV-1 formation is driven by the viral structural polyprotein Gag, which assembles at the plasma membrane into a hexagonal lattice
HIV-1 assembly is driven by the viral Gag polyprotein
The N-terminal MA domain targets Gag to the plasma membrane, where ~2,500 Gag molecules form the curved, hexagonal immature lattice of HIV-1, which is stabilized by intermolecular CA domain interactions
Summary
HIV-1 formation is driven by the viral structural polyprotein Gag, which assembles at the plasma membrane into a hexagonal lattice. Previous studies had reported that an S40F change in p6Gag impaired proteolytic maturation of Gag, reduced viral infectivity and delayed replication in T-cell lines [9,10].
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