SAMHD1: At the Crossroads of Cell Proliferation, Immune Responses, and Virus Restriction

Ballana, Ester; Esté, José A.

doi:10.1016/j.tim.2015.08.002

Cited by 79 publications

(79 citation statements)

References 85 publications

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“…As SAMHD1 is a key regulator of intracellular dNTP homeostasis (Ballana and Este, 2015), we analyzed dNTP levels in non-differentiated SAMHD1 KO and control cells by using our previously described dNTP assay (Diamond et al, 2004). Intracellular dNTP pools increased 3- to 6-fold in SAMHD1 KO compared to control cells, as shown in Fig.…”

Section: Resultsmentioning

confidence: 99%

SAMHD1 controls cell cycle status, apoptosis and HIV-1 infection in monocytic THP-1 cells

et al. 2016

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SAMHD1 limits HIV-1 infection in non-dividing myeloid cells by decreasing intracellular dNTP pools. HIV-1 restriction by SAMHD1 in these cells likely prevents activation of antiviral immune responses and modulates viral pathogenesis, thus highlighting a critical role of SAMHD1 in HIV-1 physiopathology. Here, we explored the function of SAMHD1 in regulating cell proliferation, cell cycle progression and apoptosis in monocytic THP-1 cells. Using the CRISPR/Cas9 technology, we generated THP-1 cells with stable SAMHD1 knockout. We found that silencing of SAMHD1 in cycling cells stimulates cell proliferation, redistributes cell cycle population in the G1/G0 phase and reduces apoptosis. These alterations correlated with increased dNTP levels and more efficient HIV-1 infection in dividing SAMHD1 knockout cells relative to control. Our results suggest that SAMHD1, through its dNTPase activity, affects cell proliferation, cell cycle distribution and apoptosis, and emphasize a key role of SAMHD1 in the interplay between cell cycle regulation and HIV-1 infection.

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Section: Resultsmentioning

confidence: 99%

SAMHD1 controls cell cycle status, apoptosis and HIV-1 infection in monocytic THP-1 cells

et al. 2016

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“…Target recognition requires additional substrate receptors; for CRL4 these are collectively termed DDB1- and CUL4-associated factors (DCAFs), one of which is DDB2. Notably DCAF1 is also known as Vpr binding protein; binding of the HIV-1 accessory protein Vpr to DCAF1 mediates degradation of repair factors such as helicase-like transcription factor (HLTF) and uracil DNA glycosylase (UNG2) [159,160]; similarly, HIV-2 Vpx degrades the host restriction factor SAMHD1 [161]. …”

Section: Evidence For a Connection Between Hbv And The Host Dna Damentioning

confidence: 99%

A Role for the Host DNA Damage Response in Hepatitis B Virus cccDNA Formation—and Beyond?

Schreiner

Nassal

2017

Viruses

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Chronic hepatitis B virus (HBV) infection puts more than 250 million people at a greatly increased risk to develop end-stage liver disease. Like all hepadnaviruses, HBV replicates via protein-primed reverse transcription of a pregenomic (pg) RNA, yielding an unusually structured, viral polymerase-linked relaxed-circular (RC) DNA as genome in infectious particles. Upon infection, RC-DNA is converted into nuclear covalently closed circular (ccc) DNA. Associating with cellular proteins into an episomal minichromosome, cccDNA acts as template for new viral RNAs, ensuring formation of progeny virions. Hence, cccDNA represents the viral persistence reservoir that is not directly targeted by current anti-HBV therapeutics. Eliminating cccDNA will thus be at the heart of a cure for chronic hepatitis B. The low production of HBV cccDNA in most experimental models and the associated problems in reliable cccDNA quantitation have long hampered a deeper understanding of cccDNA molecular biology. Recent advancements including cccDNA-dependent cell culture systems have begun to identify select host DNA repair enzymes that HBV usurps for RC-DNA to cccDNA conversion. While this list is bound to grow, it may represent just one facet of a broader interaction with the cellular DNA damage response (DDR), a network of pathways that sense and repair aberrant DNA structures and in the process profoundly affect the cell cycle, up to inducing cell death if repair fails. Given the divergent interactions between other viruses and the DDR it will be intriguing to see how HBV copes with this multipronged host system.

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“…maintaining genome stability [5][6][7] . Mutations in TREX1 , RNASEH2A (ribonuclease H2, subunit A), RNASEH2B (ribonuclease H2, subunit B), RNASEH2C (ribonuclease H2, subunit C), and SAMHD1 result in Aicardi-Goutières syndrome with overwhelming type I interferon-mediated autoimmunity [8][9][10] .…”

mentioning

confidence: 99%

DNA-Sensing and Nuclease Gene Expressions as Markers for Colorectal Cancer Progression

Yang¹,

Huang

Chang

et al. 2016

Oncology

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Objective: Oncogene-driven stress-related DNA damage has been observed in lesions of colon cancer. Furthermore, DNA sensors and nucleases are stimulated during active DNA damage and replication. However, their changes and influences with respect to cancer remain largely unknown. Methods: The gene expression levels of cGAS, IFI16, STING, TBK1, IFNB1, TREX1, SAMHD1, RNASEH2A, RNASEH2B, and RNASEH2C were examined in the paired colorectal cancer and adjacent normal part tissues of 53 patients. Their associations with the clinical stages of cancer were then analyzed. Results: All cytosolic DNA-sensing and nuclease-related genes except cGAS, RNASEH2A, and RNASEH2B showed lower mRNA expressions in the colorectal tumor tissues. Moreover, cGAS upregulation was found to be associated with early-stage colorectal cancers, while higher expressions of RNASEH2B, RNASEH2C, and SAMHD1 correlated with metastasis. RNASEH2C knockdown in a colon cancer cell line impaired cell migration, and analysis of the cancer RNA-seq data from The Cancer Genome Atlas (TCGA) database revealed a negative correlation between RNASEH2C expression and E-cadherin levels. Conclusions: In contrast to DNA-sensing events in viral infections or autoimmunity, cGAS-STING-IFNB signaling is disrupted in colorectal cancer. The expression levels of cGAS, RNASEH2B, RNASEH2C, and SAMHD1 could be prognostic markers of colorectal cancer.

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SAMHD1: At the Crossroads of Cell Proliferation, Immune Responses, and Virus Restriction

Cited by 79 publications

References 85 publications

SAMHD1 controls cell cycle status, apoptosis and HIV-1 infection in monocytic THP-1 cells

SAMHD1 controls cell cycle status, apoptosis and HIV-1 infection in monocytic THP-1 cells

A Role for the Host DNA Damage Response in Hepatitis B Virus cccDNA Formation—and Beyond?

DNA-Sensing and Nuclease Gene Expressions as Markers for Colorectal Cancer Progression

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