Journal Article

Zika virus prM protein contains cholesterol binding motifs required for virus entry and assembly

Prasad, Vibhu, Lozach, Pierre-Yves, Vattulainen, Ilpo, Denolly, Solène, Haselmann, Uta, Universität Heidelberg [Heidelberg] = Heidelberg University, Brügger, Britta, Lavacca, Teresa, M, Bartenschlager, Ralf, Kulig, Waldemar, Infections Virales et Pathologie Comparée - UMR 754 (IVPC) ; École Pratique des Hautes Études (EPHE) ; Université Paris Sciences et Lettres (PSL)-Université Paris Sciences et Lettres (PSL)-Université Claude Bernard Lyon 1 (UCBL) ; Université de Lyon-Université de Lyon-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), Witte, Leander, ANR-21-CE11-0012,HENIPHASE,Séparations et transitions de phase par les protéines V et W des Henipavirus: mécanismes moléculaires et implications pour leurs fonctions et pour la pathogenèse, ANR-11-IDEX-0007,Avenir L.S.E.,PROJET AVENIR LYON SAINT-ETIENNE, Mizzon, Giulia, Uckeley, Zina, M, Eu, Sungmin, ANR-22-CE15-0034,VERSATILE,Variants émergents du SRAS-CoV-2 : intersection des voies d'entrée et des réponses antivirales, Univers

2023

Overview

Abstract For successful infection of host cells and virion production, enveloped viruses, including Zika virus (ZIKV), extensively rely on cellular lipids. However, how virus protein–lipid interactions contribute to the viral life cycle remains unclear. Here, we employ a chemo-proteomics approach with a bifunctional cholesterol probe and show that cholesterol is closely associated with the ZIKV structural protein prM. Bioinformatic analyses, reverse genetics alongside with photoaffinity labeling assays, and atomistic molecular dynamics simulations identified two functional cholesterol binding motifs within the prM transmembrane domain. Loss of prM–cholesterol association has a bipartite effect reducing ZIKV entry and leading to assembly defects. We propose a model in which membrane-resident M facilitates cholesterol-supported lipid exchange during endosomal entry and, together with cholesterol, creates a platform promoting virion assembly. In summary, we identify a bifunctional role of prM in the ZIKV life cycle by mediating viral entry and virus assembly in a cholesterol-dependent manner.

• Publisher: Nature Publishing Group,CCSD,Nature Publishing Group UK,Nature Portfolio
• Subject: 13/1 / 13/106 / 13/109 / 14/19 / 14/28 / 38/109 / 38/77 / 38/88 / 38/90 / 631/326/596/2557 / 631/45/287/1197 / 82/29 / 82/80 / Assembly / Binding / Cholesterol / Genetics / Humanities and Social Sciences / Life cycles / Life Sciences / Lipids / Microbiology and Parasitology / Molecular dynamics / multidisciplinary / Photoaffinity labeling / PrM protein / Proteins / Proteomics / Science / Science (multidisciplinary) / Vector-borne diseases / Virions / Virology / Viruses / Zika virus