Cell entry of Borna disease virus follows a clathrin-mediated endocytosis pathway that requires Rab5 and microtubules

J Virol. 2009 Oct;83(20):10406-16. doi: 10.1128/JVI.00990-09. Epub 2009 Aug 5.

Abstract

Borna disease virus (BDV), the prototypic member of the Bornaviridae family within the order Mononegavirales, exhibits high neurotropism and provides an important and unique experimental model system for studying virus-cell interactions within the central nervous system. BDV surface glycoprotein (G) plays a critical role in virus cell entry via receptor-mediated endocytosis, and therefore, G is a critical determinant of virus tissue and cell tropism. However, the specific cell pathways involved in BDV cell entry have not been determined. Here, we provide evidence that BDV uses a clathrin-mediated, caveola-independent cell entry pathway. We also show that BDV G-mediated fusion takes place at an optimal pH of 6.0 to 6.2, corresponding to an early-endosome compartment. Consistent with this finding, BDV cell entry was Rab5 dependent but Rab7 independent and exhibited rapid fusion kinetics. Our results also uncovered a key role for microtubules in BDV cell entry, whereas the integrity and dynamics of actin cytoskeleton were not required for efficient cell entry of BDV.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Borna Disease / virology
  • Borna disease virus / genetics
  • Borna disease virus / metabolism
  • Borna disease virus / pathogenicity*
  • Cell Line
  • Chlorocebus aethiops
  • Clathrin / metabolism
  • Clathrin / pharmacology
  • Endocytosis*
  • Host-Pathogen Interactions*
  • Humans
  • Microtubules / metabolism*
  • Oligodendroglia / virology*
  • Vero Cells
  • Virus Internalization
  • rab5 GTP-Binding Proteins / genetics
  • rab5 GTP-Binding Proteins / metabolism*

Substances

  • Clathrin
  • rab5 GTP-Binding Proteins