The role of cellular factors in promoting HIV budding

Abstract

Human immunodeficiency virus type 1 (HIV-1) becomes enveloped while budding through the plasma membrane, and the release of nascent virions requires a membrane fission event that separates the viral envelope from the cell surface. To facilitate this crucial step in its life cycle, HIV-1 exploits a complex cellular membrane remodeling and fission machinery known as the endosomal sorting complex required for transport (ESCRT) pathway. HIV-1 Gag directly interacts with early-acting components of this pathway, which ultimately triggers the assembly of the ESCRT-III membrane fission complex at viral budding sites. Surprisingly, HIV-1 requires only a subset of ESCRT-III components, indicating that the membrane fission reaction that occurs during HIV-1 budding differs in crucial aspects from topologically related cellular abscission events.

Figure 1

Model of ESCRT-III-mediated HIV-1 release. (A) HIV-1 Gag assembles into a plasma membrane-covered spherical protein shell that protrudes from the cell surface. The engagement of the ESCRT machinery by L domains in the C-terminal p6 domain of Gag leads to the assembly of an ESCRT-III tube with a dome-like membrane binding surface within the neck of the budding virion. The presence of a curved membrane-binding surface causes constriction of the bud neck until spontaneous fission occurs. (B) In vitro assembled CHMP2A-CHMP3 tubes exhibiting a dome-like cap. (Reprinted from Lata et al.)