Virology

Replication Restricted

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Science  24 Feb 2012:
Vol. 335, Issue 6071, pp. 892
DOI: 10.1126/science.335.6071.892-c
CREDIT: ISTOCKPHOTO.COM

Despite its deadly nature, HIV-1 is quite limited in the types of cells that it can infect. HIV-1 primarily infects CD4+ T cells but not many myloid-derived immune cells. This is because most myeloid-derived cells express the viral restriction factor SAMHD1. Although this may seem like an advantage to the host, the virus actually gains the upper hand because it can escape detection by the innate immune system. In support of this, HIV-2 and some SIV strains that do not cause such severe pathology express Vpx, which counteracts the effects of SAMHD1. Little is known, however, about how SAMHD1 prevents HIV-1 infections from taking hold. Lahouassa et al. noted that SAMHD1 shares homology with a protein from Enterococcus fecalis that has nucleotide metabolism activity. Using a variety of in vitro analyses, they found that SAMHD1 exhibited phosphohydrolase activity for dNTPs and regulated the pool of dNTPs in myeloid-derived cells. SAMHD1 expression lowered the concentration of dNTPs below what is required for productive reverse transcription by HIV-1, thereby blocking infection. Thus, regulation of nucleotide pools may be a means by which cells regulate their susceptibility to viral infection, but hidden benefits for the virus may be lurking, too.

Nat. Immunol. 13, 10.1038/ni.2236 (2012).

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