HIV-1 matrix-envelope interaction in virus infectivity

Wednesday, October 26, 2011 — Poster Session IV
2:00 p.m. – 4:00 p.m.	Natcher Conference Center	NCI	VIROL/MICRO-21

Authors

• P Tedbury
• A Joshi
• E Freed

Abstract

The HIV-1 matrix (MA) domain is the principle Gag component responsible for the localization of Pr55Gag precursor to the plasma membrane. It has been reported that the Lys residues at positions 29 and 31 are important for the binding of Gag to phosphatidylinositol-4,5-bisphosphate [PI(4,5)P2]; this binding triggers a myristyl switch, exposing the myristic acid moiety which inserts into the membrane. Mutation of these Lys residues to Glu (29KE/31KE) prevents PI(4,5)P2 binding and retargets Gag to intracellular multivesicular bodies (MVBs), leading to a reduction in virus release efficiency in HeLa cells and, by an as yet unknown mechanism, loss of virus infectivity. Compensatory mutations to 29KE/31KE can be selected which ameliorate the release defect, although these mutants remain impaired for infectivity. We have looked at these mutants and the capacity of exogenous envelope proteins and the HIV-1 envelope to restore infectivity. We have also looked for compensatory mutations to fully restore infectivity. This study provides novel insights into the role of MA in particle infectivity, suggesting that mutations in MA can affect Env function and potentially interactions between Env and other components of the virion.

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