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Evidence for IFN?-induced, SAMHD1-independent inhibitors of early HIV-1 infection.


ABSTRACT:

Background

Type I interferon (IFN) treatment of some cells, including dendritic cells, macrophages and monocytic THP-1 cells, restricts HIV-1 infection and prevents viral cDNA accumulation. Sterile alpha motif and HD domain protein 1 (SAMHD1), a dGTP-regulated deoxynucleotide triphosphohydrolase, reduces HIV-1 infectivity in myeloid cells, likely by limiting dNTPs available for reverse transcription, and has been described as IFN?-inducible. Myeloid cell infection by HIV-1 is enhanced by HIV-2/SIVSM Vpx, which promotes SAMHD1 degradation, or by exogenous deoxyribonucleoside (dN) addition.

Findings

SAMHD1 expression was not substantially influenced by IFN? treatment of monocyte-derived macrophages or THP-1 cells. The contributions of SAMHD1 to the inhibition of HIV-1 infectivity by IFN? were assessed through the provision of Vpx, exogenous dN addition, or via RNAi-mediated SAMHD1 knock-down. Both Vpx and dN efficiently restored infection in IFN?-treated macrophages, albeit not to the levels seen with these treatments in the absence of IFN?. Similarly using differentiated THP-1 cells, the addition of Vpx or dNs, or SAMHD1 knock-down, also stimulated infection, but failing to match the levels observed without IFN?. Neither Vpx addition nor SAMHD1 knock-down reversed the IFN?-induced blocks to HIV-1 infection seen in dividing U87-MG or THP-1 cells. Therefore, altered SAMHD1 expression or function cannot account for the IFN?-induced restriction to HIV-1 infection seen in many cells and cell lines.

Conclusion

IFN? establishes an anti-HIV-1 phenotype in many cell types, and appears to accomplish this without potentiating SAMHD1 function. We conclude that additional IFN?-induced suppressors of the early stages of HIV-1 infection await identification.

SUBMITTER: Goujon C 

PROVIDER: S-EPMC3598776 | biostudies-literature | 2013 Feb

REPOSITORIES: biostudies-literature

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Publications

Evidence for IFNα-induced, SAMHD1-independent inhibitors of early HIV-1 infection.

Goujon Caroline C   Schaller Torsten T   Galão Rui Pedro RP   Amie Sarah M SM   Kim Baek B   Olivieri Kevin K   Neil Stuart J D SJ   Malim Michael H MH  

Retrovirology 20130225


<h4>Background</h4>Type I interferon (IFN) treatment of some cells, including dendritic cells, macrophages and monocytic THP-1 cells, restricts HIV-1 infection and prevents viral cDNA accumulation. Sterile alpha motif and HD domain protein 1 (SAMHD1), a dGTP-regulated deoxynucleotide triphosphohydrolase, reduces HIV-1 infectivity in myeloid cells, likely by limiting dNTPs available for reverse transcription, and has been described as IFNα-inducible. Myeloid cell infection by HIV-1 is enhanced by  ...[more]

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