title: Structural gene (prME) chimeras of St Louis encephalitis virus and West Nile virus exhibit altered in vitro cytopathic and growth phenotypes.
abstract: Despite utilizing the same avian hosts and mosquito vectors, St Louis encephalitis virus (SLEV) and West Nile virus (WNV) display dissimilar vector-infectivity and vertebrate-pathogenic phenotypes. SLEV exhibits a low oral infection threshold for Culex mosquito vectors and is avirulent in avian hosts, producing low-magnitude viraemias. In contrast, WNV is less orally infective to mosquitoes and elicits high-magnitude viraemias in a wide range of avian species. In order to identify the genetic determinants of these different phenotypes and to assess the utility of mosquito and vertebrate cell lines for recapitulating in vivo differences observed between these viruses, reciprocal WNV and SLEV pre-membrane and envelope protein (prME) chimeric viruses were generated and growth of these mutant viruses was characterized in mammalian (Vero), avian (duck) and mosquito [Aedes (C6/36) and Culex (CT)] cells. In both vertebrate lines, WNV grew to 100-fold higher titres than SLEV, and growth and cytopathogenicity phenotypes, determined by chimeric phenotypes, were modulated by genetic elements outside the prME gene region. Both chimeras exhibited distinctive growth patterns from those of SLEV in C6/36 cells, indicating the role of both structural and non-structural gene regions for growth in this cell line. In contrast, growth of chimeric viruses was indistinguishable from that of virus containing homologous prME genes in CT cells, indicating that structural genetic elements could specifically dictate growth differences of these viruses in relevant vectors. These data provide genetic insight into divergent enzootic maintenance strategies that could also be useful for the assessment of emergence mechanisms of closely related flaviviruses.
authors.affiliation: Center for Vector-borne Disease Research and Department of Pathology, Microbiology and Immunology, School of Veterinary Medicine, University of California, Davis, CA 95616, USA.|Division of Vector-Borne Diseases, Centers for Disease Control and Prevention (CDC), Fort Collins, CO 80521, USA.
authors.forename: Payal D
authors.initials: PD
authors.lastname: Maharaj
authors.affiliation: Center for Vector-borne Disease Research and Department of Pathology, Microbiology and Immunology, School of Veterinary Medicine, University of California, Davis, CA 95616, USA.|Division of Vector-Borne Diseases, Centers for Disease Control and Prevention (CDC), Fort Collins, CO 80521, USA.
authors.forename: Michael
authors.initials: M
authors.lastname: Anishchenko
authors.affiliation: Center for Vector-borne Disease Research and Department of Pathology, Microbiology and Immunology, School of Veterinary Medicine, University of California, Davis, CA 95616, USA.
authors.forename: Stanley A
authors.initials: SA
authors.lastname: Langevin
authors.affiliation: Center for Vector-borne Disease Research and Department of Pathology, Microbiology and Immunology, School of Veterinary Medicine, University of California, Davis, CA 95616, USA.
authors.forename: Ying
authors.initials: Y
authors.lastname: Fang
authors.affiliation: Center for Vector-borne Disease Research and Department of Pathology, Microbiology and Immunology, School of Veterinary Medicine, University of California, Davis, CA 95616, USA.
authors.forename: William K
authors.initials: WK
authors.lastname: Reisen
authors.affiliation: Center for Vector-borne Disease Research and Department of Pathology, Microbiology and Immunology, School of Veterinary Medicine, University of California, Davis, CA 95616, USA.|Division of Vector-Borne Diseases, Centers for Disease Control and Prevention (CDC), Fort Collins, CO 80521, USA.
authors.forename: Aaron C
authors.initials: AC
authors.lastname: Brault
mesh_terms: D000330:Aedes; D020816:Amino Acid Motifs; D000595:Amino Acid Sequence; D000818:Animals; D002460:Cell Line; D002678:Chimera / Q000235:genetics / Q000254:growth & development* / Q000502:physiology; D009033:Culicidae; D003588:Cytopathogenic Effect, Viral; D004372:Ducks; D004665:Encephalitis Virus, St. Louis / Q000737:chemistry / Q000235:genetics / Q000254:growth & development* / Q000502:physiology; D004674:Encephalitis, St. Louis / Q000821:virology*; D019143:Evolution, Molecular; D006801:Humans; D008969:Molecular Sequence Data; D016415:Sequence Alignment; D014759:Viral Envelope Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D014901:West Nile Fever / Q000821:virology*; D014902:West Nile virus / Q000737:chemistry / Q000235:genetics / Q000254:growth & development* / Q000502:physiology
chemical_list: D014759:Viral Envelope Proteins; C074932:prM protein, Flavivirus