ArticlePLoS pathogens2025
Cell-free assays reveal that the HIV-1 capsid protects reverse transcripts from cGAS immune sensing.
Article in PLoS pathogens, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 13 papers.
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Who cites it
13 citing papers in PubMed.
- The Central Pore of HIV-1 Capsomers Promotes Sustained Stability of the Viral Capsid.Journal of molecular biology · 2026Article
- ESCRT-III assembles around mis-segregated DNA to protect genome stability.Nature structural & molecular biology · 2026Article
- HIV-1 uncoating location dictates sites of integration.Nature communications · 2026Article
- Review
- Damaging the conical morphology of HIV-1 capsid by targeting the FG-binding pocket and disfavoring pentameric subunits needed for core closure.bioRxiv : the preprint server for biology · 2026Article
- Restraint of Powassan virus replication by TRIM5α facilitates viral avoidance of antiviral immunity.bioRxiv : the preprint server for biology · 2026Article
- Recurrent and novel evolutionary pathways drive in vitro HIV-1 lenacapavir resistance with diverse phenotypic consequences.Nature communications · 2026Article
- Host restriction factors and p17-Driven inflammaging in HIV-1: From molecular pathogenesis to functional cure.AIMS microbiology · 2026Review
- Lenacapavir-induced capsid damage uncovers HIV-1 genomes emanating from nuclear speckles.The EMBO journal · 2026Article
- Research progress on HIV-1 structural proteins and antiviral therapies.Frontiers in immunology · 2026Review
- HIV-1 and Its Strategy for Hiding Viral cDNA from STING-Mediated Innate Immunity.International journal of molecular sciences · 2025Review
- Structural and mechanistic bases for resistance of the M66I capsid variant to lenacapavir.mBio · 2025Article
- Immunomodulatory biomaterials in HIV-1 infection prevention, control and treatment.Frontiers in immunology · 2025Review
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Authors and funding
13 authors.
Funding
Abstract
Retroviruses can be detected by the innate immune sensor cyclic GMP-AMP synthase (cGAS), which recognizes reverse-transcribed DNA and activates an antiviral response. However, the extent to which HIV-1 shields its genome from cGAS recognition remains unclear. To study this process in mechanistic detail, we reconstituted reverse transcription, genome release, and innate immune sensing of HIV-1 in a cell-free system. We found that wild-type HIV-1 capsids protect viral genomes from cGAS even after completing reverse transcription. Viral DNA could be "deprotected" by thermal stress, capsid mutations, or reduced concentrations of inositol hexakisphosphate (IP6) that destabilize the capsid. Strikingly, the capsid inhibitor lenacapavir also disrupted viral cores and dramatically potentiated cGAS activity, both in vitro and in cellular infections. Our results provide biochemical evidence that the HIV-1 capsid lattice conceals the genome from cGAS and that chemical or physical disruption of the viral core can expose HIV-1 DNA and activate innate immune signaling.
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