title: Cell entry of Borna disease virus follows a clathrin-mediated endocytosis pathway that requires Rab5 and microtubules.
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.
authors: Department of Immunology and Microbial Science, The Scripps Research Institute, La Jolla, California 92037, USA.
authors: Roberto
authors: R
authors: Clemente
authors: Juan C
authors: JC
authors: de la Torre
mesh_terms: D000818:Animals; D001890:Borna Disease / Q000821:virology; D001891:Borna disease virus / Q000235:genetics / Q000378:metabolism / Q000472:pathogenicity*; D002460:Cell Line; D002522:Chlorocebus aethiops; D002966:Clathrin / Q000378:metabolism / Q000494:pharmacology; D004705:Endocytosis; D054884:Host-Pathogen Interactions; D006801:Humans; D008870:Microtubules / Q000378:metabolism*; D009836:Oligodendroglia / Q000821:virology*; D014709:Vero Cells; D053586:Virus Internalization; D020696:rab5 GTP-Binding Proteins / Q000235:genetics / Q000378:metabolism*
chemical_list: D002966:Clathrin; D020696:rab5 GTP-Binding Proteins