ArticleNature medicine2014
The ribonuclease activity of SAMHD1 is required for HIV-1 restriction.
Article in Nature medicine, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 177 papers, 1 of them a synthesis that pooled it.
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Who cites it
177 citing papers in PubMed, 1 synthesis or guideline pooled it, 267 citations in OpenAlex.
- Identification of novel HIV-1 dependency factors in primary CCR4(+)CCR6(+)Th17 cells via a genome-wide transcriptional approach.Retrovirology · 2015Pooled it
- The factory enters the fray: how mitochondrial protein trafficking shapes the host response to infection.Journal of virology · 2026Review
- ssDNA and ssRNA Promote Phase Condensation of SAMHD1.Biochemistry · 2025Article
- HIV-1 latency: From acquaintance to confidant.Journal of virus eradication · 2025Review
- Anatomical, subset, and HIV-dependent expression of viral sensors and restriction factors.Cell reports · 2025Article
- HIV controllers: hope for a functional cure.Frontiers in immunology · 2025Review
- SAMHD1 deficiency enhances macrophage-mediated clearance ofFrontiers in immunology · 2025Article
- Review
- IFI27 inhibits HIV-1 replication by degrading Gag protein through the ubiquitin-proteasome pathway.Journal of virology · 2024Article
- Human papillomavirus 16 replication converts SAMHD1 into a homologous recombination factor and promotes its recruitment to replicating viral DNA.Journal of virology · 2024Article
- Article
- Review
- Article
- Article
- May I Help You with Your Coat? HIV-1 Capsid Uncoating and Reverse Transcription.International journal of molecular sciences · 2024Review
- Advances in HIV Gene Therapy.International journal of molecular sciences · 2024Review
- Impaired influenza A virus replication by the host restriction factor SAMHD1 which inhibited by PA-mediated dephosphorylation of the host transcription factor IRF3.Virology journal · 2024Article
- Interactions between HIV proteins and host restriction factors: implications for potential therapeutic intervention in HIV infection.Frontiers in immunology · 2024Review
- Review
- Guanine-containing ssDNA and RNA induce dimeric and tetrameric structural forms of SAMHD1.Nucleic acids research · 2023Article
117 more citing papers are in PubMed but not listed here.
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Authors and funding
16 authors at 4 institutions in 2 countries.
Funding
Abstract
The HIV-1 restriction factor SAM domain- and HD domain-containing protein 1 (SAMHD1) is proposed to inhibit HIV-1 replication by depleting the intracellular dNTP pool. However, phosphorylation of SAMHD1 regulates its ability to restrict HIV-1 without decreasing cellular dNTP levels, which is not consistent with a role for SAMHD1 dNTPase activity in HIV-1 restriction. Here, we show that SAMHD1 possesses RNase activity and that the RNase but not the dNTPase function is essential for HIV-1 restriction. By enzymatically characterizing Aicardi-Goutières syndrome (AGS)-associated SAMHD1 mutations and mutations in the allosteric dGTP-binding site of SAMHD1 for defects in RNase or dNTPase activity, we identify SAMHD1 point mutants that cause loss of one or both functions. The RNase-positive and dNTPase-negative SAMHD1D137N mutant is able to restrict HIV-1 infection, whereas the RNase-negative and dNTPase-positive SAMHD1Q548A mutant is defective for HIV-1 restriction. SAMHD1 associates with HIV-1 RNA and degrades it during the early phases of cell infection. SAMHD1 silencing in macrophages and CD4(+) T cells from healthy donors increases HIV-1 RNA stability, rendering the cells permissive for HIV-1 infection. Furthermore, phosphorylation of SAMHD1 at T592 negatively regulates its RNase activity in cells and impedes HIV-1 restriction. Our results reveal that the RNase activity of SAMHD1 is responsible for preventing HIV-1 infection by directly degrading the HIV-1 RNA.
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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.