ArticlePLoS pathogens2026
NSUN2-mediated m5C modification of HIV-1 RNA enables evasion of RIG‑I‑dependent innate immunity.
Article in PLoS pathogens, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.
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11 authors.
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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.
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