Unintegrated HIV-1 DNA recruits cGAS via its histone-binding domain to escape innate immunity

• 成果类型: Article
• 署名作者: Jahan, Cyprien; Bonnet-Madin, Lucie; Machida, Shinichi; Sobhian, Bijan; Thenin-Houssier, Suzie; Benkirane, Monsef
• 署名单位: Centre National de la Recherche Scientifique (CNRS); CNRS - National Institute for Biology (INSB); Universite de Montpellier; Japan Institute for Health Security (JIHS); National Center for Global Health & Medicine - Japan
• 刊物名称: PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
• ISSN/ISSBN: 0027-11757
• DOI: 10.1073/pnas.2424465122
• 发表日期: 2025-03-18
• 关键词: activation

摘要

To ensure optimal replication and spread, viruses have evolved countermeasures to evade type 1 IFN-mediated antiviral activity.During the early viral replication cycle steps until uncoating, the HIV-1 core protects viral pathogen associated molecular patterns (viral RNA and reverse transcription products) from recognition by innate immune sensors, including cGAS. However, after capsid uncoating, unintegrated viral DNA (uvDNA) becomes accessible. Here, we show that HIV-1 uses chromatin-mediated cGAS inactivation as a mechanism to protect its uvDNA from innate immune activation.