Abstract
The SAMHD1 protein is an HIV-1 restriction factor that is targeted by the HIV-2 accessory protein Vpx in myeloid lineage cells. Mutations in the SAMHD1 gene cause Aicardi-Goutières syndrome, a genetic disease that mimics congenital viral infection. To determine the physiological function of the SAMHD1 protein, the SAMHD1 gene was cloned, recombinant protein was produced, and the catalytic activity of the purified enzyme was identified. We show that SAMHD1 contains a dGTP-regulated deoxynucleotide triphosphohydrolase. We propose that Vpx targets SAMHD1 for degradation in a viral strategy to control cellular deoxynucleotide levels for efficient replication.
Publication types
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Research Support, N.I.H., Extramural
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Research Support, Non-U.S. Gov't
MeSH terms
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Animals
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Autoimmune Diseases / genetics
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Autoimmune Diseases / metabolism
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Autoimmune Diseases of the Nervous System / genetics*
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Catalysis
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Cattle
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Deoxyguanine Nucleotides / chemistry
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Dose-Response Relationship, Drug
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HIV-1 / genetics*
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HIV-1 / metabolism
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Humans
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Mice
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Monomeric GTP-Binding Proteins / chemistry
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Monomeric GTP-Binding Proteins / genetics*
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Myeloid Cells / cytology*
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Nervous System Malformations / genetics*
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Nucleosides / chemistry
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Phosphoric Monoester Hydrolases / chemistry
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SAM Domain and HD Domain-Containing Protein 1
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Viral Regulatory and Accessory Proteins / metabolism*
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Virus Replication
Substances
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Deoxyguanine Nucleotides
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Nucleosides
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VPX protein, Human immunodeficiency virus 2
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Viral Regulatory and Accessory Proteins
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deoxyguanosine triphosphate
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Phosphoric Monoester Hydrolases
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SAM Domain and HD Domain-Containing Protein 1
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SAMHD1 protein, human
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Samhd1 protein, mouse
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Monomeric GTP-Binding Proteins
Supplementary concepts
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Aicardi-Goutieres syndrome