ArticleThe Journal of biological chemistry2015
Mechanistic and Kinetic Differences between Reverse Transcriptases of Vpx Coding and Non-coding Lentiviruses.
Article in The Journal of biological chemistry, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 21 papers.
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Who cites it
21 citing papers in PubMed, 26 citations in OpenAlex.
- Review
- Molecular Biology and Diversification of Human Retroviruses.Frontiers in virology (Lausanne, Switzerland) · 2022Article
- SAMHD1 … and Viral Ways around It.Viruses · 2021Review
- Enhanced enzyme kinetics of reverse transcriptase variants cloned from animals infected with SIVmac239 lacking viral protein X.The Journal of biological chemistry · 2020Article
- Mechanistic cross-talk between DNA/RNA polymerase enzyme kinetics and nucleotide substrate availability in cells: Implications for polymerase inhibitor discovery.The Journal of biological chemistry · 2020Review
- Review
- SAMHD1 Functions and Human Diseases.Viruses · 2020Review
- Article
- Effect of induced dNTP pool imbalance on HIV-1 reverse transcription in macrophages.Retrovirology · 2019Article
- Tyrosine Kinase Inhibition: a New Perspective in the Fight against HIV.Current HIV/AIDS reports · 2019Review
- Conserved Herpesvirus Protein Kinases Target SAMHD1 to Facilitate Virus Replication.Cell reports · 2019Article
- Host and Viral Factors Influencing Interplay between the Macrophage and HIV-1.Journal of neuroimmune pharmacology : the official journal of the Society on NeuroImmune Pharmacology · 2019Review
- Specific reverse transcriptase slippage at the HIV ribosomal frameshift sequence: potential implications for modulation of GagPol synthesis.Nucleic acids research · 2017Article
- Fidelity of classwide-resistant HIV-2 reverse transcriptase and differential contribution of K65R to the accuracy of HIV-1 and HIV-2 reverse transcriptases.Scientific reports · 2017Article
- Cell-Free versus Cell-to-Cell Infection by Human Immunodeficiency Virus Type 1 and Human T-Lymphotropic Virus Type 1: Exploring the Link among Viral Source, Viral Trafficking, and Viral Replication.Journal of virology · 2016Review
- Macrophages in Progressive Human Immunodeficiency Virus/Simian Immunodeficiency Virus Infections.Journal of virology · 2016Review
- Discovery, characterization, and lead optimization of 7-azaindole non-nucleoside HIV-1 reverse transcriptase inhibitors.Bioorganic & medicinal chemistry letters · 2016Article
- HIV-1 and HIV-2 exhibit divergent interactions with HLTF and UNG2 DNA repair proteins.Proceedings of the National Academy of Sciences of the United States of America · 2016Article
- Macrophages and HIV-1: An Unhealthy Constellation.Cell host & microbe · 2016Review
- Phylogenetic Insights into the Functional Relationship between Primate Lentiviral Reverse Transcriptase and Accessory Proteins Vpx/Vpr.Frontiers in microbiology · 2016Article
Corrections and comments
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Authors and funding
5 authors at 3 institutions in 2 countries.
Funding
Abstract
Among lentiviruses, HIV Type 2 (HIV-2) and many simian immunodeficiency virus (SIV) strains replicate rapidly in non-dividing macrophages, whereas HIV Type 1 (HIV-1) replication in this cell type is kinetically delayed. The efficient replication capability of HIV-2/SIV in non-dividing cells is induced by a unique, virally encoded accessory protein, Vpx, which proteasomally degrades the host antiviral restriction factor, SAM domain- and HD domain-containing protein 1 (SAMHD1). SAMHD1 is a dNTPase and kinetically suppresses the reverse transcription step of HIV-1 in macrophages by hydrolyzing and depleting cellular dNTPs. In contrast, Vpx, which is encoded by HIV-2/SIV, kinetically accelerates reverse transcription by counteracting SAMHD1 and then elevating cellular dNTP concentration in non-dividing cells. Here, we conducted the pre-steady-state kinetic analysis of reverse transcriptases (RTs) from two Vpx non-coding and two Vpx coding lentiviruses. At all three sites of the template tested, the two RTs of the Vpx non-coding viruses (HIV-1) displayed higher kpol values than the RTs of the Vpx coding HIV-2/SIV, whereas there was no significant difference in the Kd values of these two groups of RTs. When we employed viral RNA templates that induce RT pausing by their secondary structures, the HIV-1 RTs showed more efficient DNA synthesis through pause sites than the HIV-2/SIV RTs, particularly at low dNTP concentrations found in macrophages. This kinetic study suggests that RTs of the Vpx non-coding HIV-1 may have evolved to execute a faster kpol step, which includes the conformational changes and incorporation chemistry, to counteract the limited dNTP concentration found in non-dividing cells and still promote efficient viral reverse transcription.
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