title: Structural proteins of West Nile virus are a major determinant of infectious particle production and fitness in astrocytes.
abstract: The molecular basis for the increased resistance of astrocytes to a non-neuropathogenic strain of West Nile virus (WNV), WNV-MAD78, compared with the neuropathogenic strain WNV-NY remains unclear. Here, we demonstrated that the reduced susceptibility of astrocytes to WNV-MAD78 is due to a combination of both cellular activities as well as viral determinants. Analyses of the viral particle indicated that astrocyte-derived WNV-MAD78 particles were less infectious than those of WNV-NY. Additionally, inhibition of cellular furin-like proteases increased WNV-MAD78 infectious particle production in astrocytes, suggesting that high levels of furin-like protease activity within these cells acted in a cell- and strain-specific manner to inhibit WNV-MAD78 replication. Moreover, analysis of recombinant viruses indicated that the structural proteins of WNV-MAD78 were responsible for decreased particle infectivity and the corresponding reduction in infectious particle production compared with WNV-NY. Thus, the composition of the WNV virion was also a major determinant for viral fitness within astrocytes and may contribute to WNV propagation within the central nervous system. Whether the WNV-MAD78 structural genes reduce virus replication and particle infectivity through the same mechanism as the cellular furin-like protease activity or whether these two determinants function through distinct pathways remains to be determined.
authors.affiliation: Department of Cell Biology and Molecular Genetics, University of Maryland, College Park, MD 20742, USA.
authors.forename: Katherine L
authors.initials: KL
authors.lastname: Hussmann
authors.affiliation: Department of Cell Biology and Molecular Genetics, University of Maryland, College Park, MD 20742, USA.
authors.forename: Rianna
authors.initials: R
authors.lastname: Vandergaast
authors.affiliation: Department of Cell Biology and Molecular Genetics, University of Maryland, College Park, MD 20742, USA.
authors.forename: Kang
authors.initials: K
authors.lastname: Zheng
authors.affiliation: Department of Cell Biology and Molecular Genetics, University of Maryland, College Park, MD 20742, USA.
authors.forename: Lisa I
authors.initials: LI
authors.lastname: Hoover
authors.affiliation: Maryland Pathogen Research Institute, University of Maryland, College Park, MD 20742, USA.|Department of Cell Biology and Molecular Genetics, University of Maryland, College Park, MD 20742, USA.
authors.forename: Brenda L
authors.initials: BL
authors.lastname: Fredericksen
mesh_terms: D000818:Animals; D001253:Astrocytes / Q000201:enzymology* / Q000276:immunology / Q000821:virology*; D002460:Cell Line; D002490:Central Nervous System / Q000821:virology; D002522:Chlorocebus aethiops; D045683:Furin / Q000037:antagonists & inhibitors / Q000378:metabolism; D006031:Glycosylation; D006801:Humans; D014709:Vero Cells; D015678:Viral Structural Proteins / Q000276:immunology*; D014779:Virus Replication / Q000235:genetics*; D014901:West Nile Fever / Q000821:virology; D014902:West Nile virus / Q000235:genetics / Q000276:immunology / Q000472:pathogenicity*
chemical_list: D015678:Viral Structural Proteins; D045683:Furin