
==== Front
bioRxiv
BIORXIV
bioRxiv
2692-8205
Cold Spring Harbor Laboratory

10.1101/2024.09.05.611432
preprint
1
Article
PIP2 promotes the incorporation of CD43, PSGL-1 and CD44 into nascent HIV-1 particles
Cardoso Ricardo de Souza
Murakami Tomoyuki
Jacobovitz Binyamin
Veatch Sarah L. http://orcid.org/0000-0002-9317-2308

Ono Akira http://orcid.org/0000-0001-7841-851X

05 9 2024
2024.09.05.611432https://creativecommons.org/licenses/by-nc-nd/4.0/ This work is licensed under a Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International License, which allows reusers to copy and distribute the material in any medium or format in unadapted form only, for noncommercial purposes only, and only so long as attribution is given to the creator.
http://biorxiv.org/lookup/doi/10.1101/2024.09.05.611432
nihpp-2024.09.05.611432.pdf
Abstract

Determinants regulating sorting of host transmembrane proteins at sites of enveloped virus assembly on the plasma membrane (PM) remain poorly understood. Here, we demonstrate for the first time that PM acidic phospholipid PIP2 regulates such sorting into an enveloped virus, HIV-1. Incorporation of CD43, PSGL-1, and CD44 into HIV-1 particles is known to have profound effects on viral spread; however, the mechanisms promoting their incorporation were unknown. We found that depletion of cellular PIP2 blocks the incorporation of CD43, PSGL-1, and CD44 into HIV-1 particles. Expansion microscopy revealed that PIP2 depletion diminishes nanoscale co-clustering between viral structural protein Gag and the three transmembrane proteins at PM and that Gag induces PIP2 enrichment around itself. CD43, PSGL-1, and CD44 also increased local PIP2 density, revealing their PIP2 affinity. Altogether, these results support a new mechanism where local enrichment of an acidic phospholipid drives co-clustering between viral structural and cellular transmembrane proteins, thereby modulating the content, and hence the fate, of progeny virus particles.
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pmc
