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Human metapneumovirus small hydrophobic (SH) protein downregulates type I IFN pathway signaling by affecting STAT1

Andrew K Hastings1, Katherine R Amato2, Sherry C Wen1

  • 1Department of Pathology, Microbiology & Immunology, Vanderbilt University School of Medicine, Nashville, TN 37232, United States.

Virology
|May 1, 2016
PubMed

Insights

Human metapneumovirus (HMPV) uses its small hydrophobic (SH) protein to block antiviral immunity. The SH protein inhibits signal transducer and activator of transcription-1 (STAT1) phosphorylation, a key step in interferon signaling.

Area of Science:

  • Virology
  • Immunology
  • Cell Biology

Background:

  • Type I interferons (IFNs) are crucial for antiviral defense.
  • Human metapneumovirus (HMPV) is known to interfere with IFN signaling pathways.
  • HMPV lacks known viral antagonists of IFN signaling.

Purpose of the Study:

  • To investigate the mechanism by which HMPV inhibits type I IFN signaling.
  • To identify the specific viral protein responsible for this inhibition.
  • To determine if HMPV targets signal transducer and activator of transcription-1 (STAT1).

Main Methods:

  • Comparing STAT1 phosphorylation in HMPV-infected and mock-infected cells.
  • Utilizing transient overexpression of HMPV proteins, specifically the small hydrophobic (SH) protein.
  • Generating and testing a recombinant HMPV lacking the SH protein.

Main Results:

  • HMPV infection impaired STAT1 expression and phosphorylation in response to type I IFN.
  • Overexpression of HMPV SH protein significantly inhibited STAT1 phosphorylation and downstream signaling.
  • A recombinant HMPV lacking the SH protein failed to inhibit STAT1 phosphorylation.

Conclusions:

  • The small hydrophobic (SH) protein of HMPV plays a critical role in downregulating type I IFN signaling.
  • HMPV SH protein targets STAT1, thereby inhibiting the antiviral immune response.
  • This mechanism represents a novel strategy employed by HMPV to evade host immunity.
Keywords:
InterferonMetapneumovirusParamyxovirusSmall hydrophobic protein

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