ArticleProceedings of the National Academy of Sciences of the United States of America2022
Human endogenous retrovirus-K (HERV-K) reverse transcriptase (RT) structure and biochemistry reveals remarkable similarities to HIV-1 RT and opportunities for HERV-K-specific inhibition.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 34 papers.
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Who cites it
34 citing papers in PubMed, 37 citations in OpenAlex.
- Human Endogenous Retroviruses in Myalgic Encephalomyelitis/Chronic Fatigue Syndrome: Emerging Roles in Pathogenesis, Immunity, Biomarkers and Therapeutics.International journal of molecular sciences · 2026Review
- Nucleoside-Analog Reverse-Transcriptase Inhibitors (NRTIs) Against Multiple Sclerosis: Comprehensive Review on a Possible Novel Therapeutic Approach.Neurology international · 2026Review
- Aberrant Expression of Human Endogenous Retroviruses andInternational journal of molecular sciences · 2026Article
- Metagenomic analysis of bacterial and viral communities of Aedes aegypti and Aedes albopictus.Journal, genetic engineering & biotechnology · 2026Article
- Review
- Estrogen-Driven Breast Carcinogenesis in a Rat Model is Linked to Retroelement Activation and Inflammation and is Susceptible to Lamivudine Treatment.Breast cancer (Dove Medical Press) · 2026Article
- Mechanism for Nucleotidyl Transfer in LINE-1 ORF2p Revealed by QM/MM Simulations.International journal of molecular sciences · 2025Article
- MicroRNAs in HIV infection: dual regulators of viral replication and host immunity.Naunyn-Schmiedeberg's archives of pharmacology · 2025Review
- Mechanism and spectrum of inhibition of viral polymerases by 2'-deoxy-2'-β-fluoro-4'-azidocytidine or azvudine.NAR molecular medicine · 2025Article
- Sequence Diversity and Encoded Enzymatic Differences of Monocistronic L1 ORF2 mRNA Variants in the Aged Normal and Alzheimer's Disease Brain.The Journal of neuroscience : the official journal of the Society for Neuroscience · 2025Article
- Patients with Irritable Bowel Syndrome Exhibit Aberrant Expression of Endogenous Retroviruses and SETDB1.Cells · 2025Article
- Next-Generation Sequencing Methods to Determine the Accuracy of Retroviral Reverse Transcriptases: Advantages and Limitations.Viruses · 2025Review
- Reliable Polymerase Chain Reaction Methods for Screening for Porcine Endogenous Retroviruses-C (PERV-C) in Pigs.Viruses · 2025Article
- Enhanced Transcription of Human Endogenous Retroviruses and TRIM28 Downregulation in Patients with Inflammatory Bowel Disease.Viruses · 2024Article
- Mutant IDH1 inhibition induces dsDNA sensing to activate tumor immunity.Science (New York, N.Y.) · 2024Article
- Subcellular location of L1 retrotransposon-encoded ORF1p, reverse transcription products, and DNA sensors in lupus granulocytes.Mobile DNA · 2024Article
- Nucleoside Reverse Transcriptase Inhibitor Exposure Is Associated with Lower Alzheimer's Disease Risk: A Retrospective Cohort Proof-of-Concept Study.Pharmaceuticals (Basel, Switzerland) · 2024Article
- Development of human endogenous retrovirus type K- related treatments for human diseases.Journal of medical virology · 2024Review
- Article
- Lamivudine, Doravirine, and Cabotegravir Downregulate the Expression of Human Endogenous Retroviruses (HERVs), Inhibit Cell Growth, and Reduce Invasive Capability in Melanoma Cell Lines.International journal of molecular sciences · 2024Article
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Authors and funding
11 authors at 3 institutions in 3 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Human endogenous retroviruses (HERVs) comprise nearly 8% of the human genome and are derived from ancient integrations of retroviruses into the germline. The biology of HERVs is poorly defined, but there is accumulating evidence supporting pathological roles in diverse diseases, such as cancer, autoimmune, and neurodegenerative diseases. Functional proteins are produced by HERV-encoded genes, including reverse transcriptases (RTs), which could be a contributor to the pathology attributed to aberrant HERV-K expression. To facilitate the discovery and development of HERV-K RT potent and selective inhibitors, we expressed active HERV-K RT and determined the crystal structure of a ternary complex of this enzyme with a double-stranded DNA substrate. We demonstrate a range of RT inhibition with antiretroviral nucleotide analogs, while classic nonnucleoside analogs do not inhibit HERV-K RT. Detailed comparisons of HERV-K RT with other known RTs demonstrate similarities to diverse RT families and a striking similarity to the HIV-1 RT asymmetric heterodimer. Our analysis further reveals opportunities for selective HERV-K RT inhibition.
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