ArticleRetrovirology2014
Kinetic variations between reverse transcriptases of viral protein X coding and noncoding lentiviruses.
Article in Retrovirology, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 17 papers.
What it found
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Who cites it
17 citing papers in PubMed, 21 citations in OpenAlex.
- Host cell restriction factors of equine infectious anemia virus.Virologica Sinica · 2023Review
- Antiretroviral Treatment of HIV-2 Infection: Available Drugs, Resistance Pathways, and Promising New Compounds.International journal of molecular sciences · 2023Review
- Review
- 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
- SAMHD1 Functions and Human Diseases.Viruses · 2020Review
- Article
- Intertwined: SAMHD1 cellular functions, restriction, and viral evasion strategies.Medical microbiology and immunology · 2019Review
- Incomplete Suppression of HIV-1 by SAMHD1 Permits Efficient Macrophage Infection.Pathogens & immunity · 2018Article
- Article
- 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
- Phylogenetic Insights into the Functional Relationship between Primate Lentiviral Reverse Transcriptase and Accessory Proteins Vpx/Vpr.Frontiers in microbiology · 2016Article
- Mechanistic and Kinetic Differences between Reverse Transcriptases of Vpx Coding and Non-coding Lentiviruses.The Journal of biological chemistry · 2015Article
- Article
- Intrinsic host restrictions to HIV-1 and mechanisms of viral escape.Nature immunology · 2015Review
Corrections and comments
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Authors and funding
5 authors at 4 institutions in 2 countries.
Funding
Abstract
backgroundHost SAM domain and HD domain-containing protein 1 (SAMHD1) suppresses reverse transcription kinetics of HIV-1 in nondividing cells such as macrophages by hydrolyzing and nearly depleting cellular dNTPs, which are the substrates of viral reverse transcriptase (RT). However, unlike HIV-1, HIV-2 and SIVsm encode viral protein X (Vpx), which counteracts the dNTPase activity of SAMHD1 and elevates dNTP concentration, allowing the viruses to replicate under abundant dNTP conditions even in nondividing cells.
findingsHere we tested whether RTs of these Vpx coding and noncoding lentiviruses display different enzyme kinetic profiles in response to dNTP concentrations. For this test, we characterized an extensive collection of RTs from 7 HIV-1 strains, 4 HIV-2 strains and 7 SIV strains, and determined their steady-state kinetic parameters. The K m values of all HIV-1 RTs were consistently low and close to the low dNTP concentrations found in macrophages. However, the K m values of SIV and HIV-2 RTs were not only higher than those of HIV-1 RTs but also varied significantly, indicating that HIV-2/SIV RTs require higher dNTP concentrations for efficient DNA synthesis, compared to HIV-1 RT. However, the k cat values of all eighteen lentiviral RTs were very similar.
conclusionsOur biochemical analysis supports the hypothesis that the enzymological properties, particularly, K m values, of lentivirus RTs, are mechanistically tied with the cellular dNTP availability in nondividing target cells, which is controlled by SAMHD1 and Vpx.
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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.