Ask about this productRelated genes to: SAMHD1 Blocking Peptide
- Gene:
- SAMHD1 NIH gene
- Name:
- SAM and HD domain containing deoxynucleoside triphosphate triphosphohydrolase 1
- Previous symbol:
- -
- Synonyms:
- SBBI88, Mg11, HDDC1, MOP-5, AGS5
- Chromosome:
- 20q11.23
- Locus Type:
- gene with protein product
- Date approved:
- 2001-07-31
- Date modifiied:
- 2019-04-23
Related products to: SAMHD1 Blocking Peptide
Related articles to: SAMHD1 Blocking Peptide
- Obesity has become a serious global public health challenge, characterized by chronic, sterile, low-grade inflammation with excessive NLRP3 inflammasome activation; however, the mechanism underlying the reduced activation threshold remains unclear. A recent study by Liu et al. demonstrated that obesity induces the phosphorylation and inactivation of SAMHD1, leading to a massive accumulation of cytosolic dNTPs. This causes excess dNTPs to enter mitochondria via the PNC1/2 transporters, bypassing the classical CMPK2 salvage synthesis pathway and triggering uncontrolled mtDNA synthesis and oxidative damage, ultimately resulting in the excessive activation of NLRP3 and an inflammatory response. Based on this finding, this paper presents a "double-edged sword" model of nucleotide metabolic reprogramming in obesity-related inflammation. Early reversible inactivation of SAMHD1 may represent a metabolic adaptive response that confers functional benefits to macrophages; however, once metabolic stress persists and causes nucleotide metabolic reprogramming to exceed a yet-to-be-defined threshold, an inflammatory positive feedback loop may be established. In terms of clinical translation, targeting PNC1/2 could specifically inhibit NLRP3 activation, which may provide new upstream intervention strategies for various aseptic inflammatory conditions such as gout; however, this approach also carries potential risks of mitochondrial toxicity and impaired anti-infective immunity. Future efforts should focus on macrophage-specific delivery, precision interventions tailored to disease stages, and precise anti-inflammatory strategies based on biomarkers such as circulating dNTPs, p-SAMHD1, and ox-mtDNA, thereby advancing the clinical translation of metabolism-related inflammation within safe parameters. - Source: PubMed
Publication date: 2026/09/26
Li ZijingLiu YushangOuyang XinyeWu WenjuanWang Maoyuan - Sterile alpha motif and histidine-aspartate domain-containing protein 1 (SAMHD1) is a dNTPase that depletes intracellular dNTP pools in nondividing cells such as human monocyte-derived macrophages (MDMs). These low dNTP levels suppress HIV-1 reverse transcription kinetics in MDMs. In contrast, viral protein X (Vpx), an accessory protein encoded by human immunodeficiency virus type 2 (HIV-2) and some simian immunodeficiency viruses (SIVs), induces degradation of SAMHD1, thereby increasing cellular dNTP pools and promoting a more permissive infection in MDMs. Our previous study demonstrated that the central polypurine tract (cPPT) facilitates completion of HIV-1 reverse transcription, particularly when reverse transcription is kinetically delayed due to dNTP limitation in nondividing human lung fibroblasts. However, the role of cPPT during HIV-1 replication in macrophages where SAMHD1 establishes low dNTP pools and kinetically restricts viral reverse transcription remains untested. To address this question, we performed time-course analyses of transduction efficiency and fluorescence intensity in MDMs transduced with two distinct HIV-1 vector systems containing or lacking the cPPT sequence, in the presence or absence of Vpx. Our data show that while either cPPT insertion or Vpx treatment alone modestly increases HIV-1 vector transduction efficiency, the combined presence of cPPT and Vpx results in a pronounced enhancement of both transduction efficiency and fluorescence intensity in MDMs. Overall, these findings demonstrate that cPPT and Vpx act cooperatively to enhance HIV-1 vector transduction in nondividing MDMs, supporting an interplay between cPPT function and Vpx-mediated SAMHD1 degradation in macrophages. - Source: PubMed
Publication date: 2026/09/10
Alvarez Natalie NBurke Hannah SFreeman TzipporahTaki SaraLi QunSchinazi Raymond FKim Baek - Although eosinophils are accepted as transcriptionally heterogeneous in asthma, how allergic inflammation shapes eosinophil states during influenza A virus (IAV) infection remains undefined. We integrated high-resolution single-cell RNA sequencing, spatial transcriptomics, quantitative immunofluorescence imaging, and cell-cell communication analyses to profile murine lungs across naïve, asthma, influenza (Flu), and Asthma+Flu conditions. We identified three related eosinophil transcriptional states distributed along a disease-associated continuum. Eosinophils in the Flu-only condition preferentially expressed canonical antiviral and interferon-stimulated genes including Isg15, Gbp2, Samhd1, whilst Asthma+Flu eosinophils showed attenuated induction of these programs together with enrichment of genes associated with chemotaxis, adhesion, inflammatory regulation, and metabolic remodeling. Asthma+Flu eosinophils were also enriched for a human asthma-associated EosHigh gene signature. A progressive shift in eosinophils from antigen-presenting programs toward chemotactic and tissue remodeling-associated states as identified by pseudotime analysis may imply a changing functional emphasis rather than sustained canonical antiviral activation. Spatial profiling confirmed condition-dependent eosinophil abundance, increased eosinophil Alox15 expression in allergic conditions, and disease-specific cellular neighborhoods. Cross-platform analyses identified recurrent predicted interactions between eosinophils and a distinct Alox15+ alveolar macrophage population. Mast cells adopted infection-specific IL-1 and leukocyte-activation transcriptional programs without major compositional changes. Collectively, these findings demonstrate that the T2 microenvironment reshapes both the transcriptional state and spatial organization of lung eosinophils during IAV infection, providing an integrated framework for understanding eosinophil heterogeneity and cellular coordination in the allergic lungs. - Source: PubMed
Publication date: 2026/09/08
Veltri Anthony JWells Anthony JBaus MagdalineMathur Sameer KSamarasinghe Amali E - We present a patient with complex symptoms, including those consistent with familial chilblain lupus (FCL). A de novo likely pathogenic variant in explains observed microcephaly, sensorineural hearing loss, growth restriction, and mild dysmorphism, but not perniosis with acral autoamputation, small joint arthritis, and immune abnormalities. Transcriptomics revealed a type I IFN signature and strong downregulation of , which is associated with a spectrum of interferonopathies, including FCL. RNA reads from only the first 4 exons of were detectable, with no coverage of exon 5 onward. Subsequent long-read genome sequencing identified a homozygous, balanced, reciprocal translocation from the locus on chromosome 20 (q11.23) to chromosome 17 (p11.2). Utilizing an iterative genetic testing approach encompassing exomic, transcriptional, and genomic readouts was invaluable for elucidating the uncommon structural variation carried by this patient. Autozygous balanced, reciprocal translocations are extremely rare, and this appears to be the first case of any inborn error of immunity attributed to this mode of inheritance. - Source: PubMed
Publication date: 2026/08/26
Baker Paul JZhang YaoyuanBishop ImogenCleveland Madeline LMcAllan Alexandra LHollway Georgina EVedururu RavikiranKumar AmitKrishnaswamy RajWan Ken LKaub Peter ABrown Emma LNarayanan Dhanya LakshmiDeveson Ira W Gowdie PeterRenton William DOjaimi SamarFennell Andrew PMasters Seth L - Sulforaphane (SFN), a natural compound found in cruciferous vegetables, mobilizes the transcription factor NRF2 to protect macrophages from HIV-1. SFN/NRF2 exerts this protective effect by promoting the reduced phosphorylation of the antiviral protein SAMHD1. Phosphorylation at threonine 592 (T592) potently inhibits the capacity of SAMHD1 to restrict HIV-1. How SFN, and other NRF2 mobilizers reduce SAMHD1 T592 phosphorylation is unclear. p21 (CDKN1A) is an NRF2-responsive protein that accumulates in primary macrophages after SFN treatment. p21 blocks SAMHD1 T592 phosphorylation through the inhibition of several cyclin-dependent kinases. We therefore hypothesized that SFN acts through p21 to reduce SAMHD1 T592 phosphorylation in macrophages. Here, we use RNAi, CRISPR-Cas9, and pharmacological inhibition to deplete or delete p21 in macrophages and demonstrate that p21 is necessary for SFN to efficiently reduce SAMHD1 T592 phosphorylation and restrict HIV-1 transduction. - Source: PubMed
Publication date: 2026/08/20
Marcelino Bianka Nicolle PenaGirard KierstenLetourneau LaurenLewin AndrewLewin DavidPresicci AnnaReistrom LukeWilliams TylerSharifi H John