Inhibition of spumavirus gene expression by PHF11

PLoS Pathogens
Melissa KanePaul D Bieniasz

Abstract

The foamy viruses (FV) or spumaviruses are an ancient subfamily of retroviruses that infect a variety of vertebrates. FVs are endemic, but apparently apathogenic, in modern non-human primates. Like other retroviruses, FV replication is inhibited by type-I interferon (IFN). In a previously described screen of IFN-stimulated genes (ISGs), we identified the macaque PHD finger domain protein-11 (PHF11) as an inhibitor of prototype foamy virus (PFV) replication. Here, we show that human and macaque PHF11 inhibit the replication of multiple spumaviruses, but are inactive against several orthoretroviruses. Analysis of other mammalian PHF11 proteins revealed that antiviral activity is host species dependent. Using multiple reporter viruses and cell lines, we determined that PHF11 specifically inhibits a step in the replication cycle that is unique to FVs, namely basal transcription from the FV internal promoter (IP). In so doing, PHF11 prevents expression of the viral transactivator Tas and subsequent activation of the viral LTR promoter. These studies reveal a previously unreported inhibitory mechanism in mammalian cells, that targets a family of ancient viruses and may promote viral latency.

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Citations

Apr 4, 2021·Viruses·Ananda Ayyappan Jaguva VasudevanCarsten Münk

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Datasets Mentioned

BETA
U21247
KX087159

Methods Mentioned

BETA
FACS
Infection
FCS
PCR
transfection
flow cytometry
electrophoresis

Software Mentioned

GraphPad Prism
CLC Main Workbench

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