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Interferon-induced sterile alpha motif and histidine/aspartic acid domain-containing protein 1 expression in astrocytes and microglia is mediated by microRNA-181a.

Interferon-induced sterile alpha motif and histidine/aspartic acid domain-containing protein 1 expression in astrocytes and microglia is mediated by microRNA-181a.
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Jin C, Peng X, Liu F, Cheng L, Xie T, Lu X, Wu H, Wu N,


Jin C, Peng X, Liu F, Cheng L, Xie T, Lu X, Wu H, Wu N, (click to view)

Jin C, Peng X, Liu F, Cheng L, Xie T, Lu X, Wu H, Wu N,

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AIDS (London, England) 30(13) 2053-64 doi 10.1097/QAD.0000000000001166

Abstract
OBJECTIVE
Sterile alpha motif and histidine/aspartic acid domain-containing protein 1 (SAMHD1), a newly discovered HIV-1 host restriction factor, has been found to be induced by interferons and to be regulated by microRNA-181a (miR-181a). However, the mechanism of interferons-induced SAMHD1 expression is unclear.

DESIGN
We hypothesized that interferons induce SAMHD1 expression through Janus kinase-signal transducer and activator of transcription (JAK-STAT) signaling pathways, which is mediated by miR-181a.

METHODS
We examined the effect of IFN-α and IFN-γ on SAMHD1 mRNA and protein expression, as well as the levels of phosphorylated SAMHD1 and miR-181a in astrocytes and microglia. To determine whether interferons-induced SAMHD1 expression was mediated by miR-181a, we overexpressed or inhibited miR-181a in these cells and exposed them to interferons. We also detected the effect of SAMHD1 and miR-181a on HIV-1 infection in astrocytes and microglia.

RESULTS
Both IFN-α and IFN-γ increased SAMHD1 mRNA and protein expression, and reduced miR-181a levels, particularly in microglia. Phosphorylated SAMHD1was not induced by interferons. Overexpression of miR-181a counteracted induction of SAMHD1 expression by interferons, and inhibition of miR-181a mimicked interferons treatment. Inhibition of JAK-STAT signaling pathways resulted in increased miR-181a levels and decreased SAMHD1 mRNA expression. Knock-down of SAMHD1 or overexpression of miR-181a enhanced HIV-1 infection, whereas inhibition of miR-181a reduced HIV-1 infection. However, inhibition of HIV-1 infection induced by IFN-α was not significantly affected by miR-181a and SAMHD1.

CONCLUSION
MiR-181a is an important mediator for interferons-induced SAMHD1 expression in astrocytes and microglia, but not for inhibition of HIV-1 infection induced by IFN-α.

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