ArticlemBio2024
HIV-1 capsid stability and reverse transcription are finely balanced to minimize sensing of reverse transcription products
Article in mBio, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 18 papers.
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Who cites it
18 citing papers in PubMed, 14 citations in OpenAlex.
- The Central Pore of HIV-1 Capsomers Promotes Sustained Stability of the Viral Capsid.Journal of molecular biology · 2026Article
- Capsid stabilization reprograms the nuclear fate of the HIV genome.Science advances · 2026Article
- Recurrent and novel evolutionary pathways drive in vitro HIV-1 lenacapavir resistance with diverse phenotypic consequences.Nature communications · 2026Article
- Antiviral Inflammasomes and How to Find Them.Viruses · 2026Review
- Reconstructing a Missing Link of HIV-1 Assembly: HIV-1 Envelope-Matrix Interactions in a Native Viral Context.bioRxiv : the preprint server for biology · 2026Article
- HSV-2 genome recognition by nuclear cGAS instigates IFN-β production and influences inflammasome activation duringFrontiers in immunology · 2026Article
- Use of the Split Luciferase Complementation Assay to Identify Novel Small Molecules That Disrupt Essential Protein-Protein Interactions of Viruses.Biomolecules · 2025Article
- HIV-1 and Its Strategy for Hiding Viral cDNA from STING-Mediated Innate Immunity.International journal of molecular sciences · 2025Review
- Considerations for capsid-targeting antiretrovirals in pre-exposure prophylaxis.Trends in molecular medicine · 2025Review
- Reverse transcription progression and genome length regulate HIV-1 core elasticity and disassembly.PLoS pathogens · 2025Article
- Lenacapavir disrupts HIV-1 core integrity while stabilizing the capsid lattice.Proceedings of the National Academy of Sciences of the United States of America · 2025Article
- Unintegrated HIV-1 DNA recruits cGAS via its histone-binding domain to escape innate immunity.Proceedings of the National Academy of Sciences of the United States of America · 2025Article
- Article
- HIV capsids: orchestrators of innate immune evasion, pathogenesis and pandemicity.The Journal of general virology · 2025Review
- Cell-free assays reveal that the HIV-1 capsid protects reverse transcripts from cGAS immune sensing.PLoS pathogens · 2025Article
- A basally active cGAS-STING pathway limits SARS-CoV-2 replication in a subset of ACE2 positive airway cell models.Nature communications · 2024Article
- A basally active cGAS-STING pathway limits SARS-CoV-2 replication in a subset of ACE2 positive airway cell models.bioRxiv : the preprint server for biology · 2024Article
- May I Help You with Your Coat? HIV-1 Capsid Uncoating and Reverse Transcription.International journal of molecular sciences · 2024Review
Corrections and comments
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Authors and funding
8 authors at 1 institution in 1 country.
Funding
Abstract
A critical determinant for early post-entry events, the HIV-1 capsid (CA) protein forms the conical core when it rearranges around the dimeric RNA genome and associated viral proteins. Although mutations in CA have been reported to alter innate immune sensing of HIV-1, a direct link between core stability and sensing of HIV-1 nucleic acids has not been established. Herein, we assessed how manipulating the stability of the CA lattice through chemical and genetic approaches affects innate immune recognition of HIV-1. We found that destabilization of the CA lattice resulted in potent sensing of reverse transcription products when destabilization IMPORTANCE: In HIV-1 particles, the dimeric RNA genome and associated viral proteins and enzymes are encased in a proteinaceous lattice composed of the viral capsid protein. Herein, we assessed how altering the stability of this capsid lattice through orthogonal genetic and chemical approaches impacts the induction of innate immune responses. Specifically, we found that decreasing capsid lattice stability results in more potent sensing of viral reverse transcription products, but not the genomic RNA, in a cGAS-STING-dependent manner. The recently developed capsid inhibitors lenacapavir and GS-CA1 enhanced the innate immune sensing of HIV-1. Unexpectedly, due to increased levels of reverse transcription and cytosolic accumulation of the resulting viral cDNA, capsid mutants with hyperstable cores also resulted in the potent induction of type I interferon-mediated innate immunity. Our findings suggest that HIV-1 capsid lattice stability and reverse transcription are finely balanced to minimize exposure of reverse transcription products in the cytosol of host cells.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.