RT Journal Article SR Electronic(1) A1 Hussmann, Katherine L. A1 Vandergaast, Rianna A1 Zheng, Kang A1 Hoover, Lisa I. A1 Fredericksen, Brenda L.YR 2014 T1 Structural proteins of West Nile virus are a major determinant of infectious particle production and fitness in astrocytes JF Journal of General Virology, VO 95 IS 9 SP 1991 OP 2003 DO https://doi.org/10.1099/vir.0.065474-0 PB Microbiology Society, SN 1465-2099, AB 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., UL https://www.microbiologyresearch.org/content/journal/jgv/10.1099/vir.0.065474-0