ArticleRetrovirology2011
Inhibition of HIV-1 infection by TNPO3 depletion is determined by capsid and detectable after viral cDNA enters the nucleus.
Article in Retrovirology, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 73 papers, 1 of them a synthesis that pooled it.
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Who cites it
73 citing papers in PubMed, 1 synthesis or guideline pooled it, 97 citations in OpenAlex.
- HIV Genome-Wide Protein Associations: a Review of 30 Years of Research.Microbiology and molecular biology reviews : MMBR · 2016Pooled it
- Monitoring HIV-1 Nuclear Import Kinetics Using a Chemically Induced Nuclear Pore Blockade Assay.Methods in molecular biology (Clifton, N.J.) · 2024Article
- Characterization of Megabat-Favored, CA-Dependent Susceptibility to Retrovirus Infection.Journal of virology · 2023Article
- Complex Relationships between HIV-1 Integrase and Its Cellular Partners.International journal of molecular sciences · 2022Review
- Transportin-3 Facilitates Uncoating of Influenza A Virus.International journal of molecular sciences · 2022Article
- CRISPR/Cas9-Induced Mutagenesis Corroborates the Role of Transportin-SR2 in HIV-1 Nuclear Import.Microbiology spectrum · 2021Article
- HIV-1 capsid variability: viral exploitation and evasion of capsid-binding molecules.Retrovirology · 2021Review
- Inhibition of autophagy rescues muscle atrophy in a LGMDD2 Drosophila model.FASEB journal : official publication of the Federation of American Societies for Experimental Biology · 2021Article
- The Role of Capsid in the Early Steps of HIV-1 Infection: New Insights into the Core of the Matter.Viruses · 2021Review
- Highly-potent, synthetic APOBEC3s restrict HIV-1 through deamination-independent mechanisms.PLoS pathogens · 2021Article
- Role of Transportin-SR2 in HIV-1 Nuclear Import.Viruses · 2021Review
- Measuring the subcellular compartmentalization of viral infections by protein complementation assay.Proceedings of the National Academy of Sciences of the United States of America · 2021Article
- HIV-1 Hijacking of Host ATPases and GTPases That Control Protein Trafficking.Frontiers in cell and developmental biology · 2021Review
- Cell Type-Dependent Escape of Capsid Inhibitors by Simian Immunodeficiency Virus SIVcpz.Journal of virology · 2020Article
- TNPO3-Mediated Nuclear Entry of the Rous Sarcoma Virus Gag Protein Is Independent of the Cargo-Binding Domain.Journal of virology · 2020Article
- Article
- A Quantitative Genetic Interaction Map of HIV Infection.Molecular cell · 2020Article
- TRIM34 restricts HIV-1 and SIV capsids in a TRIM5α-dependent manner.PLoS pathogens · 2020Article
- Cyclophilin A protects HIV-1 from restriction by human TRIM5α.Nature microbiology · 2019Article
- Interferon-Inducible MicroRNA miR-128 Modulates HIV-1 Replication by Targeting TNPO3 mRNA.Journal of virology · 2019Article
13 more citing papers are in PubMed but not listed here.
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2 authors at 1 institution in 1 country.
Funding
Abstract
backgroundHIV-1 infects non-dividing cells. This implies that the virus traverses the nuclear pore before it integrates into chromosomal DNA. Recent studies demonstrated that TNPO3 is required for full infectivity of HIV-1. The fact that TNPO3 is a karyopherin suggests that it acts by directly promoting nuclear entry of HIV-1. Some studies support this hypothesis, while others have failed to do so. Additionally, some studies suggest that TNPO3 acts via HIV-1 Integrase (IN), and others indicate that it acts via capsid (CA).
resultsTo shed light on the mechanism by which TNPO3 contributes to HIV-1 infection we engineered a panel of twenty-seven single-cycle HIV-1 vectors each bearing a different CA mutation and characterized them for the ability to transduce cells in which TNPO3 had been knocked down (KD). Fourteen CA mutants were relatively TNPO3-independent, as compared to wild-type (WT) HIV-1. Two mutants were more TNPO3-dependent than the WT, and eleven mutants were actually inhibited by TNPO3. The efficiency of the synthesis of viral cDNA, 2-LTR circles, and proviral DNA was then assessed for WT HIV-1 and three select CA mutants. Controls included rescue of TNPO3 KD with non-targetable coding sequence, RT- and IN- mutant viruses, and pharmacologic inhibitors of RT and IN. TNPO3 KD blocked transduction and establishment of proviral DNA by wild-type HIV-1 with no significant effect on the level of 2-LTR circles. PCR results were confirmed by achieving TNPO3 KD using two different methodologies (lentiviral vector and siRNA oligonucleotide transfection); by challenging three different cell types; by using two different challenge viruses, each necessitating different sets of PCR primers; and by pseudotyping virus with VSV G or using HIV-1 Env.
conclusionTNPO3 promotes HIV-1 infectivity at a step in the virus life cycle that is detectable after the preintegration complex arrives in the nucleus and CA is the viral determinant for TNPO3 dependence.
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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.