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Inhibition of spumavirus gene expression by PHF11

Melissa Kane1,2, Vincent Mele1,2, Rachel A Liberatore3,4

  • 1Department of Pediatrics, Infectious Diseases Division, UPMC Children's Hospital of Pittsburgh, Pittsburgh, Pennsylvania, United States of America.

Plos Pathogens
|July 18, 2020
PubMed

Insights

The PHD finger protein-11 (PHF11) inhibits foamy virus (FV) replication by targeting a unique step in their life cycle. This antiviral mechanism, dependent on host species, may promote viral latency.

Area of Science:

  • Virology
  • Immunology
  • Molecular Biology

Background:

  • Foamy viruses (FVs) are an ancient retroviral subfamily found in various vertebrates.
  • FV replication is known to be inhibited by type-I interferon (IFN).
  • Previous screens identified macaque PHD finger protein-11 (PHF11) as an inhibitor of prototype foamy virus (PFV).

Purpose of the Study:

  • To investigate the antiviral activity of human and macaque PHF11 against multiple spumaviruses.
  • To determine the specificity of PHF11 inhibition against different retroviral families.
  • To elucidate the precise mechanism by which PHF11 inhibits FV replication.

Main Methods:

  • Testing the inhibitory effects of human and macaque PHF11 on various spumaviruses and orthoretroviruses.
  • Analyzing PHF11 proteins from different mammalian species for antiviral activity.
  • Utilizing reporter viruses and cell lines to pinpoint the stage of FV replication targeted by PHF11.

Main Results:

  • Human and macaque PHF11 inhibit multiple spumaviruses but not orthoretroviruses.
  • Antiviral activity of PHF11 is host species-dependent.
  • PHF11 specifically inhibits basal transcription from the FV internal promoter, preventing Tas expression and LTR activation.

Conclusions:

  • PHF11 represents a novel antiviral mechanism in mammalian cells targeting FVs.
  • PHF11's specific inhibition of FV transcription may play a role in establishing viral latency.
  • This discovery sheds light on the interaction between host factors and ancient viral families.

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