HIV-1 Gag Targeting to the Plasma Membrane Reorganizes Sphingomyelin-rich and Cholesterol-rich Lipid Domains

Overview

Journal Nat Commun

Specialty Biology

Date 2023 Nov 22

PMID 37990014

Authors

Nario Tomishige

Maaz Bin Nasim

Motohide Murate

Brigitte Pollet

Pascal Didier

Julien Godet

Ludovic Richert

Yasushi Sako

Yves Mely

Toshihide Kobayashi

Affiliations

Soon will be listed here.

Abstract

Although the human immunodeficiency virus type 1 lipid envelope has been reported to be enriched with host cell sphingomyelin and cholesterol, the molecular mechanism of the enrichment is not well understood. Viral Gag protein plays a central role in virus budding. Here, we report the interaction between Gag and host cell lipids using different quantitative and super-resolution microscopy techniques in combination with specific probes that bind endogenous sphingomyelin and cholesterol. Our results indicate that Gag in the inner leaflet of the plasma membrane colocalizes with the outer leaflet sphingomyelin-rich domains and cholesterol-rich domains, enlarges sphingomyelin-rich domains, and strongly restricts the mobility of sphingomyelin-rich domains. Moreover, Gag multimerization induces sphingomyelin-rich and cholesterol-rich lipid domains to be in close proximity in a curvature-dependent manner. Our study suggests that Gag binds, coalesces, and reorganizes pre-existing lipid domains during assembly.

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