Rho GTPase activity modulates paramyxovirus fusion protein-mediated cell-cell fusion

Rachel M Schowalter1, Mark A Wurth, Hector C Aguilar

  • 1Department of Molecular and Cellular Biochemistry, University of Kentucky, 741 South Limestone, Lexington, KY 40536-0509, USA.

Virology
|February 28, 2006
PubMed

Insights

Paramyxovirus fusion proteins mediate cell fusion, influenced by actin dynamics. Activated Rac1 and Cdc42 enhanced fusion, while RhoA had varied effects, highlighting cell-type specificity in paramyxovirus-host interactions.

Area of Science:

  • Virology
  • Cell Biology
  • Biochemistry

Background:

  • Paramyxovirus fusion (F) protein mediates viral and cell-cell fusion.
  • Actin cytoskeleton dynamics are crucial for membrane fusion but their role in paramyxovirus F-mediated fusion is not well understood.

Purpose of the Study:

  • To investigate the role of actin dynamics, regulated by Rho family GTPases, in paramyxovirus F-mediated cell-cell fusion.
  • To determine how different Rho GTPases (Rac1, Cdc42, RhoA) affect fusion mediated by Hendra and SV5 F proteins in various cell types.

Main Methods:

  • Utilized reporter gene and syncytia assays to quantify cell-cell fusion.
  • Expressed constitutively active forms of Rho family GTPases (Rac1(V12), Cdc42(V12), RhoA(L63)) in cells expressing paramyxovirus F proteins.

Main Results:

  • Rac1(V12) and Cdc42(V12) increased fusion mediated by Hendra and SV5 F proteins, with cell-type-specific effects.
  • RhoA(L63) decreased Hendra F-mediated fusion but had minimal impact on SV5 F-mediated fusion.
  • GTPase activation within the glycoprotein-expressing cell primarily influenced fusion outcomes.
  • Activated Cdc42 also promoted nuclear rearrangement within syncytia.

Conclusions:

  • Actin dynamics, modulated by specific Rho GTPases, play a significant role in paramyxovirus F-mediated cell-cell fusion.
  • The impact of Rho GTPases on fusion is dependent on both the specific GTPase and the cell type involved.
  • These findings provide insights into the complex interplay between viral fusion machinery and host cell cytoskeleton.

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