SAMHD1 is the dendritic- and myeloid-cell-specific HIV-1 restriction factor counteracted by Vpx

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p21 regulates the HIV-1 restriction factor SAMHD1.

Allouch et al. (1) have shown that CDKN1A (p21) restricts HIV-1 replication in monocyte-derived macrophages (MDM) by controlling the expression of the ribonucleotide reductase subunit R2 (RNR2) of the ribonucleotide reductase enzyme that, in turn, controls the intracellular deoxynucleotide (dNTP) pool required for HIV-1 reverse transcription. dNTP levels are also tightly controlled by the dNTP ...

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SAMHD1-Dependent and -Independent Functions of HIV-2/SIV Vpx Protein

Both human immunodeficiency virus (HIV) and simian immunodeficiency virus (SIV) encode a unique set of accessory proteins that enhance viral replication in the host. Two similar accessory proteins, Vpx and Vpr, are encoded by HIV-2. In contrast, HIV-1 encodes Vpr but not Vpx. Recent studies have indicated that Vpx counteracts a particular host restriction factor, thereby facilitating reverse tr...

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Immune Activation Influences SAMHD1 Expression and Vpx-mediated SAMHD1 Degradation during Chronic HIV-1 Infection

SAMHD1 restricts human immunodeficiency virus type 1 (HIV-1) replication in myeloid cells and CD4+ T cells, while Vpx can mediate SAMHD1 degradation to promote HIV-1 replication. Although the restriction mechanisms of SAMHD1 have been well-described, SAMHD1 expression and Vpx-mediated SAMHD1 degradation during chronic HIV-1 infection were poorly understood. Flow cytometric analysis was used to ...

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Functional analysis of the relationship between Vpx and the restriction factor SAMHD1.

SAMHD1 is a newly identified restriction factor that targets lentiviruses in myeloid cells and is countered by the SIV(SM)/HIV-2 Vpx protein. By analyzing a large panel of Vpx mutants, we identify several residues throughout the 3-helix bundle predicted for Vpx that impair both its functionality and its ability to degrade SAMHD1. We determine that SAMHD1 is a strictly non-shuttling nuclear prot...

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Aicardi-Goutieres syndrome gene and HIV-1 restriction factor SAMHD1 is a dGTP-regulated deoxynucleotide triphosphohydrolase.

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 activ...

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ژورنال

عنوان ژورنال: Nature

سال: 2011

ISSN: 0028-0836,1476-4687

DOI: 10.1038/nature10117