{
  "abstract": "Recently, 5-methylcytosine (m5C) modification has been identified in HIV-1 genomic RNA. However, the functional role of this RNA modification in the antiviral innate immune response remains unclear. Here, we demonstrate that m5C modification of HIV-1 genomic RNA enables the virus to evade the type I interferon (IFN-I)-mediated antiviral response, thereby promoting viral replication. Depletion of NSUN2 in viral-producing cells significantly reduced m5C modification of HIV-1 RNA, leading to progeny viruses that are more susceptible to innate immune detection and consequently displaying attenuated replication. Furthermore, in vitro-transcribed m5C-modified RNA exhibited a reduced ability to induce IFN-I production relative to unmodified RNA. Additionally, m5C-modified RNA displayed markedly impaired binding to RIG-I compared with unmodified RNA. Collectively, our findings reveal that HIV-1 utilizes m5C modification of viral genomic RNA as a strategy to escape RIG-I-mediated immune recognition, thereby facilitating efficient viral replication. Author summary: HIV-1 remains a major global health challenge, in part because the virus has evolved clever ways to avoid being detected by the human immune system. In our study, we set out to understand how HIV-1 evades the body’s first line of defense, known as innate immunity. We discovered that HIV-1 hijacks a human protein called NSUN2 to add a chemical mark called m5C to its own genomic RNA. This mark hides the viral RNA from RIG-I, which normally recognizes foreign RNA and triggers an antiviral response. By masking itself this way, HIV-1 can replicate more efficiently and establish infection. Our findings reveal a new strategy HIV-1 uses to evade the immune system, linking RNA chemical modifications to viral escape. This knowledge not only deepens our understanding of how HIV-1 survives in the body but also points to potential new targets for developing treatments that could help the immune system recognize and fight the virus.",
  "abstract_shown": true,
  "affiliations": [
    "Key Laboratory of Medical Molecular Virology (MOE/NHC/CAMS), Shanghai Institute of Infectious Disease and Biosecurity, School of Basic Medical Sciences, Shanghai Medical College, Fudan University, Shanghai, China",
    "Institute of Medical Virology, Taikang Medical School (School of Basic Medical Sciences), Wuhan University, Wuhan, Hubei, China"
  ],
  "article_type": "Research Article",
  "arxiv": null,
  "author_total": 11,
  "authors": [
    {
      "affs": [
        0
      ],
      "name": "Yuebo Xu"
    },
    {
      "affs": [
        1
      ],
      "name": "Mingyang Li"
    },
    {
      "name": "Yingying Song"
    },
    {
      "name": "Weili Kong"
    },
    {
      "name": "Jingjing Song"
    },
    {
      "name": "Jiali Zhang"
    },
    {
      "name": "Xinmu Xu"
    },
    {
      "name": "Haoyu Ma"
    },
    {
      "name": "Shun Yu"
    },
    {
      "name": "Shuliang Chen"
    },
    {
      "name": "Cong Zeng"
    }
  ],
  "bibtex": "https://research.draconitic.com/paper/535erc4r51x98.bib",
  "cited_by": 0,
  "doi": "10.1371/journal.ppat.1014611",
  "fulltext_url": "https://journals.plos.org/plospathogens/article?id=10.1371/journal.ppat.1014611",
  "id": "535erc4r51x98",
  "issns": [
    "1553-7374"
  ],
  "landing_url": "https://journals.plos.org/plospathogens/article?id=10.1371/journal.ppat.1014611",
  "language": null,
  "licence": "CC-BY-4.0",
  "licence_label": "CC BY 4.0",
  "licence_source": "journal",
  "licence_url": "https://creativecommons.org/licenses/by/4.0/",
  "metadata_licence": null,
  "native_subjects": [
    [
      "openalex",
      "1312|RNA modifications and cancer"
    ],
    [
      "plos",
      "/Biology and life sciences/Genetics/Genomics/Microbial genomics/Viral genomics"
    ],
    [
      "plos",
      "/Biology and life sciences/Immunology/Immune response"
    ],
    [
      "plos",
      "/Biology and life sciences/Microbiology/Medical microbiology/Microbial pathogens/Viral pathogens/Immunodeficiency viruses/HIV/HIV-1"
    ],
    [
      "plos",
      "/Biology and life sciences/Microbiology/Medical microbiology/Microbial pathogens/Viral pathogens/Retroviruses/Lentivirus/HIV/HIV-1"
    ],
    [
      "plos",
      "/Biology and life sciences/Microbiology/Microbial genomics/Viral genomics"
    ],
    [
      "plos",
      "/Biology and life sciences/Microbiology/Virology/Viral genomics"
    ],
    [
      "plos",
      "/Biology and life sciences/Microbiology/Virology/Viral replication"
    ],
    [
      "plos",
      "/Biology and life sciences/Microbiology/Virology/Viral structure/Virions"
    ],
    [
      "plos",
      "/Biology and life sciences/Molecular biology/Molecular biology techniques/Molecular biology assays and analysis techniques/Nucleic acid analysis/RNA analysis"
    ],
    [
      "plos",
      "/Biology and life sciences/Molecular biology/Molecular biology techniques/Transfection"
    ],
    [
      "plos",
      "/Biology and life sciences/Organisms/Viruses/Immunodeficiency viruses/HIV/HIV-1"
    ],
    [
      "plos",
      "/Biology and life sciences/Organisms/Viruses/RNA viruses/Retroviruses/Lentivirus/HIV/HIV-1"
    ],
    [
      "plos",
      "/Biology and life sciences/Organisms/Viruses/Viral pathogens/Immunodeficiency viruses/HIV/HIV-1"
    ],
    [
      "plos",
      "/Biology and life sciences/Organisms/Viruses/Viral pathogens/Retroviruses/Lentivirus/HIV/HIV-1"
    ],
    [
      "plos",
      "/Medicine and health sciences/Immunology/Immune response"
    ],
    [
      "plos",
      "/Medicine and health sciences/Pathology and laboratory medicine/Pathogens/Microbial pathogens/Viral pathogens/Immunodeficiency viruses/HIV/HIV-1"
    ],
    [
      "plos",
      "/Medicine and health sciences/Pathology and laboratory medicine/Pathogens/Microbial pathogens/Viral pathogens/Retroviruses/Lentivirus/HIV/HIV-1"
    ],
    [
      "plos",
      "/Research and analysis methods/Biological cultures/Cell cultures/Cultured tumor cells/HeLa cells"
    ],
    [
      "plos",
      "/Research and analysis methods/Biological cultures/Cell lines/HeLa cells"
    ],
    [
      "plos",
      "/Research and analysis methods/Molecular biology techniques/Molecular biology assays and analysis techniques/Nucleic acid analysis/RNA analysis"
    ],
    [
      "plos",
      "/Research and analysis methods/Molecular biology techniques/Transfection"
    ]
  ],
  "openalex": "W7214274868",
  "pdf_url": "https://journals.plos.org/plospathogens/article/file?id=10.1371/journal.ppat.1014611&type=printable",
  "pmcid": null,
  "pmid": null,
  "published": "2026-09-25",
  "publisher": "Public Library of Science",
  "ris": "https://research.draconitic.com/paper/535erc4r51x98.ris",
  "sources": [
    {
      "first_seen": "2026-10-30T12:17:43Z",
      "native_id": "10.1371/journal.ppat.1014611",
      "source": "plos",
      "url": "https://journals.plos.org/plospathogens/article?id=10.1371/journal.ppat.1014611"
    }
  ],
  "subjects": [
    {
      "field": "biology",
      "origin": "plos:microbiology",
      "subfield": "microbiology"
    }
  ],
  "title": "NSUN2-mediated m5C modification of HIV-1 RNA enables evasion of RIG‑I‑dependent innate immunity",
  "title_text": "NSUN2-mediated m5C modification of HIV-1 RNA enables evasion of RIG‑I‑dependent innate immunity",
  "type": "peer-reviewed",
  "updated_at": "2026-10-30T12:17:43Z",
  "url": "https://research.draconitic.com/paper/535erc4r51x98",
  "venue": "PLOS Pathogens",
  "versions": []
}