HIV-1 budding requires cortical actin disassembly by the oxidoreductase MICAL1

• 成果类型: Article
• 署名作者: Serrano, Thomas; Casartelli, Nicoletta; Ghasemi, Foad; Wioland, Hugo; Cuvelier, Frederique; Salles, Audrey; Moya-Nilges, Maryse; Welker, Lisa; Bernacchi, Serena; Ruff, Marc; Jegou, Antoine; Romet-Lemonne, Guillaume; Schwartz, Olivier; Fremont, Stephane; Echard, Arnaud
• 署名单位: Pasteur Network; Universite Paris Cite; Institut Pasteur Paris; Centre National de la Recherche Scientifique (CNRS); CNRS - National Institute for Biology (INSB); Pasteur Network; Universite Paris Cite; Institut Pasteur Paris; Universite Paris Cite; Centre National de la Recherche Scientifique (CNRS); Pasteur Network; Universite Paris Cite; Institut Pasteur Paris; Pasteur Network; Universite Paris Cite; Institut Pasteur Paris; Centre National de la Recherche Scientifique (CNRS); CNRS - National Institute for Biology (INSB); Universites de Strasbourg Etablissements Associes; Universite de Strasbourg; Institut National de la Sante et de la Recherche Medicale (Inserm); Centre National de la Recherche Scientifique (CNRS); CNRS - National Institute for Biology (INSB); Universites de Strasbourg Etablissements Associes; Universite de Strasbourg; Institut National de la Sante et de la Recherche Medicale (Inserm)
• 刊物名称: PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
• ISSN/ISSBN: 0027-10186
• DOI: 10.1073/pnas.2407835121
• 发表日期: 2024-11-19
• 关键词: f-actin; rab35 gtpase; late domain; late steps; escrt; proteins; cytoskeleton; release; tsg101; RECRUITMENT

摘要

Many enveloped viruses bud from the plasma membrane that is tightly associated with a dense and thick actin cortex. This actin network represents a significant challenge for membrane deformation and scission, and how it is remodeled during the late steps of the viral cycle is largely unknown. Using superresolution microscopy, we show that HIV- 1 buds in areas of the plasma membrane with low cortical F- actin levels. We find that the cellular oxidoreductase MICAL1 locally depolymerizes actin at budding sites to promote HIV- 1 budding and release. Upon MICAL1 depletion, F- actin abnormally remains at viral budding sites, incompletely budded viruses accumulate at the plasma membrane and viral release is impaired. Remarkably, normal viral release can be restored in MICAL1-depleted cells by inhibiting Arp2/3- dependent branched actin networks. Mechanistically, we find that MICAL1 directly disassembles branched- actin networks and controls the timely recruitment of the Endosomal Sorting Complexes Required for Transport scission machinery during viral budding. In addition, the MICAL1 activator Rab35 is recruited at budding sites, functions in the same pathway as MICAL1, and is also required for viral release. This work reveals a role for oxidoreduction in triggering local actin depolymerization to control HIV- 1 budding, a mechanism that may be widely used by other viruses. The debranching activity of MICAL1 could be involved beyond viral budding in various other cellular functions requiring local plasma membrane deformation.