ArticleScientific reports2017
GCN2 phosphorylates HIV-1 integrase and decreases HIV-1 replication by limiting viral integration.
Article in Scientific reports, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 20 papers.
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Who cites it
20 citing papers in PubMed, 30 citations in OpenAlex.
- The integrated stress response suppresses antiviral RNA interference by autophagy-mediated degradation of the RNA-induced silencing complex.Proceedings of the National Academy of Sciences of the United States of America · 2025Article
- Isolation of New Chemical Modulators of the Interaction Between HIV-1 Integrase and the Cellular Restriction Factor GCN2.Viruses · 2025Article
- Involvement of Human Cellular Proteins and Structures in Realization of the HIV Life Cycle: A Comprehensive Review, 2024.Viruses · 2024Review
- Analysis of Sigma-1 Receptor Antagonist BD1047 Effect on Upregulating Proteins in HIV-1-Infected Macrophages Exposed to Cocaine Using Quantitative Proteomics.Biomedicines · 2024Article
- Brief Histories of Retroviral Integration Research and Associated International Conferences.Viruses · 2024Review
- ATF4 Signaling in HIV-1 Infection: Viral Subversion of a Stress Response Transcription Factor.Biology · 2024Review
- Cellular Stress Responses against Coronavirus Infection: A Means of the Innate Antiviral Defense.Journal of microbiology and biotechnology · 2024Review
- General control nonderepressible 2 (GCN2) as a therapeutic target in age-related diseases.Frontiers in aging · 2024Review
- Review
- A little less aggregation a little more replication: Viral manipulation of stress granules.Wiley interdisciplinary reviews. RNA · 2023Review
- A proteomic screen of Ty1 integrase partners identifies the protein kinase CK2 as a regulator of Ty1 retrotransposition.Mobile DNA · 2022Article
- Complex Relationships between HIV-1 Integrase and Its Cellular Partners.International journal of molecular sciences · 2022Review
- First report of computational protein-ligand docking to evaluate susceptibility to HIV integrase inhibitors in HIV-infected Iranian patients.Biochemistry and biophysics reports · 2022Article
- Review
- Viperin triggers ribosome collision-dependent translation inhibition to restrict viral replication.Molecular cell · 2022Article
- Murine Norovirus Infection Results in Anti-inflammatory Response Downstream of Amino Acid Depletion in Macrophages.Journal of virology · 2021Article
- Review
- Targeting the Integrated Stress Response Kinase GCN2 to Modulate Retroviral Integration.Molecules (Basel, Switzerland) · 2021Article
- Dengue Virus Induced COX-2 Signaling Is Regulated Through Nutrient Sensor GCN2.Frontiers in immunology · 2020Article
- Post-translational Modification-Based Regulation of HIV Replication.Frontiers in microbiology · 2018Review
Corrections and comments
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Authors and funding
14 authors at 3 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
GCN2 is a serine/threonine kinase involved in cellular stress response related to amino acid starvation. Previously, we showed that GCN2 interacts with HIV-1 integrase and is activated during HIV-1 infection. Herein, we identified HIV-1 integrase as a previously unknown substrate of GCN2 in vitro with a major site of phosphorylation at residue S255 located in the C-terminal domain of HIV-1 integrase. The underlying mechanism was investigated and it appeared that the integrase active site was required in order for GCN2 to target the integrase residue S255. Moreover, various integrases from other retroviruses (e.g. MLV, ASV) were also recognized as a substrate by GCN2. In cells, HIV-1 lentiviral particles harboring mutation at integrase position 255 were affected in their replication. Preventing phosphorylation resulted in an increase in infectivity that correlated with an increase in viral DNA integration. Infectivity of MLV was also higher in cells knocked-out for GCN2 suggesting a conserved mechanism to control viral replication. Altogether, our data suggest that GCN2 may constitute a general guardian of genome stability by regulating foreign DNA integration and as such be part of the antiviral armamentarium of the cell.
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