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The Simian virus 40 late viral protein VP4 disrupts the nuclear envelope for viral release

Kristina M Giorda1, Smita Raghava, Daniel N Hebert

  • 1Department of Biochemistry and Molecular Biology, University of Massachusetts, Amherst, Massachusetts, USA.

Journal of Virology
|January 13, 2012
PubMed

Insights

Simian virus 40 (SV40) protein VP4 causes cell lysis by forming pores in the nuclear membrane. This viral protein is essential for virus release and dissemination.

Area of Science:

  • Virology
  • Cell Biology
  • Molecular Biology

Background:

  • Simian virus 40 (SV40) is a virus known to cause cell lysis.
  • The viral protein VP4 is expressed late in SV40 infection and is hypothesized to aid in virus dissemination through cell lysis.

Purpose of the Study:

  • To investigate the role of SV40 VP4 protein in cell lysis.
  • To determine the specific domains and residues of VP4 crucial for its cytolytic activity.

Main Methods:

  • Expression of VP4 in mammalian cells.
  • Treatment of cells with purified VP4.
  • Assays to assess cell membrane integrity and nuclear envelope disruption.
  • Analysis of VP4 domains and specific residues for cytolytic function.

Main Results:

  • VP4 localized to the nuclear periphery, compromising nuclear envelope integrity.
  • The central hydrophobic domain and C-terminal nuclear localization signal of VP4 were essential for cytolysis, nuclear envelope accumulation, and membrane disruption.
  • A conserved proline residue in the hydrophobic domain was critical for VP4-mediated membrane perforation and cytolytic activity.

Conclusions:

  • SV40 VP4 protein induces cell lysis by forming pores in the nuclear membrane.
  • VP4's cytolytic activity is dependent on its hydrophobic domain and nuclear localization signal.
  • These findings elucidate the mechanism of SV40-induced cell lysis and virus release.

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