C terminal CYS-RICH region of mumps virus structural V protein correlates with block of interferon alpha and gamma

T Kubota1, N Yokosawa, S Yokota

  • 1Department of Microbiology, Sapporo Medical University School of Medicine, South 1, West 16, Chou-ku, Sapporo, Hokkaido, 060-8556, Japan.

Insights

Mumps virus (MV) infection blocks interferon (IFN) signaling by decreasing STAT-1alpha. The MV V protein, specifically its cysteine-rich Vsp domain, inhibits IFN-induced antiviral states and STAT protein induction.

Area of Science:

  • Virology
  • Immunology
  • Molecular Biology

Background:

  • Interferon (IFN) signaling is crucial for antiviral responses.
  • Persistent mumps virus (MV) infection is associated with blocked IFN-alpha/gamma signal transduction.
  • Decreased STAT-1alpha levels have been observed in MV-infected cells.

Purpose of the Study:

  • To investigate the mechanism by which mumps virus interferes with IFN signaling.
  • To identify the specific viral component responsible for blocking the IFN pathway.
  • To elucidate the role of STAT proteins in MV-induced immune evasion.

Main Methods:

  • Expression of mumps virus proteins (MV-V, MV-Vsp, MV-P) in cell lines.
  • Analysis of IFN-alpha/gamma signal transduction pathway components (STAT-1alpha, STAT-2, IRF-9).
  • Transfection with expression vectors (pTM-V, pTM-Vsp) to study protein function independently.

Main Results:

  • Expression of MV-V or its C-terminal cysteine-rich region (MV-Vsp) inhibited IFN-induced antiviral states.
  • MV-P protein expression did not inhibit the antiviral state.
  • Suppression of IFN-induced STAT-1alpha, STAT-2, and IRF-9 (p48) was observed in cells expressing MV-V or MV-Vsp.

Conclusions:

  • The mumps virus V protein, particularly its cysteine-rich domain (Vsp), plays a key role in suppressing the IFN signal transduction pathway.
  • MV-V inhibits the induction of essential STAT proteins required for IFN signaling.
  • This viral mechanism contributes to immune evasion during persistent mumps virus infections.

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