HIV-1 assembly at the plasma membrane

Abstract

HIV-1 particle assembly takes place at the plasma membrane, which likely enhances release of extracellular virions and spread to next target cells. Recent work by our lab and others started to reveal a molecular mechanism by which HIV ensures to make the plasma membrane as a primary site of virus assembly.

Fig. 1

A schematic representation of HIV-1 Gag domains. Structural domains and regions that function in steps of virus assembly are shown. N-terminal myristate moiety is shown (m-).

Fig. 2

PI(4,5)P₂ facilitates Gag localization at the PM and interaction with lipid bilayer. A. HeLa cells were transfected with an HIV-1 molecular clone expressing Gag-YFP fusion protein (Gag) and an expression plasmid encoding full-length myc-tagged 5ptaseIV (FL) or its inactive deletion mutant (Δ1). Note that in cells expressing full-length 5ptaseIV, Gag localizes at perinuclear compartments but not at the PM. B. [³⁵S]-labeled WT or 29KE/31KE Gag was synthesized by the in vitro transcription/translation system using rabbit reticulocyte lysates and incubated with liposomes containing indicated lipid components for 90 min. The mixture was subjected to membrane flotation centrifugation. Membrane (memb.)- and non-membrane (non-memb.)-bound Gag was quantified by phosphorimager analysis. PC, phosphatidylcholine; PS, phosphatidylserine.

Fig. 3

A proposed model for MA-PI(4,5)P2 interaction and lipid raft association. A model proposed based on the NMR results [32] is depicted. Adapted from Reference [55].