title: West Nile Virus Temperature Sensitivity and Avian Virulence Are Modulated by NS1-2B Polymorphisms.
abstract: West Nile virus (WNV) replicates in a wide variety of avian species, which serve as reservoir and amplification hosts. WNV strains isolated in North America, such as the prototype strain NY99, elicit a highly pathogenic response in certain avian species, notably American crows (AMCRs; Corvus brachyrhynchos). In contrast, a closely related strain, KN3829, isolated in Kenya, exhibits a low viremic response with limited mortality in AMCRs. Previous work has associated the difference in pathogenicity primarily with a single amino acid mutation at position 249 in the helicase domain of the NS3 protein. The NY99 strain encodes a proline residue at this position, while KN3829 encodes a threonine. Introduction of an NS3-T249P mutation in the KN3829 genetic background significantly increased virulence and mortality; however, peak viremia and mortality were lower than those of NY99. In order to elucidate the viral genetic basis for phenotype variations exclusive of the NS3-249 polymorphism, chimeric NY99/KN3829 viruses were created. We show herein that differences in the NS1-2B region contribute to avian pathogenicity in a manner that is independent of and additive with the NS3-249 mutation. Additionally, NS1-2B residues were found to alter temperature sensitivity when grown in avian cells.
authors.affiliation: Division of Vector-Borne Diseases, Centers for Disease Control and Prevention, Fort Collins, Colorado, United States of America.
authors.forename: Elizabeth A
authors.initials: EA
authors.lastname: Dietrich
authors.affiliation: Department of Pathology, Microbiology and Immunology, School of Veterinary Medicine, University of California, Davis, Davis, California, United States of America.
authors.forename: Stanley A
authors.initials: SA
authors.lastname: Langevin
authors.affiliation: Division of Vector-Borne Diseases, Centers for Disease Control and Prevention, Fort Collins, Colorado, United States of America.
authors.forename: Claire Y-H
authors.initials: CY
authors.lastname: Huang
authors.affiliation: Department of Pathology, Microbiology and Immunology, School of Veterinary Medicine, University of California, Davis, Davis, California, United States of America.
authors.forename: Payal D
authors.initials: PD
authors.lastname: Maharaj
authors.affiliation: Division of Vector-Borne Diseases, Centers for Disease Control and Prevention, Fort Collins, Colorado, United States of America.
authors.forename: Mark J
authors.initials: MJ
authors.lastname: Delorey
authors.affiliation: Department of Biomedical Sciences, Colorado State University, Fort Collins, Colorado, United States of America.
authors.forename: Richard A
authors.initials: RA
authors.lastname: Bowen
authors.affiliation: Division of Vector-Borne Diseases, Centers for Disease Control and Prevention, Fort Collins, Colorado, United States of America.
authors.forename: Richard M
authors.initials: RM
authors.lastname: Kinney
authors.affiliation: Division of Vector-Borne Diseases, Centers for Disease Control and Prevention, Fort Collins, Colorado, United States of America.
authors.forename: Aaron C
authors.initials: AC
authors.lastname: Brault
mesh_terms: D000818:Animals; D001715:Bird Diseases / Q000821:virology; D001717:Birds / Q000821:virology*; D007630:Kenya / Q000453:epidemiology; D009154:Mutation; D009656:North America / Q000453:epidemiology; D011110:Polymorphism, Genetic; D013696:Temperature; D017361:Viral Nonstructural Proteins / Q000235:genetics*; D014766:Viremia; D014774:Virulence / Q000235:genetics; D014779:Virus Replication; D014901:West Nile Fever / Q000453:epidemiology / Q000821:virology; D014902:West Nile virus / Q000235:genetics* / Q000472:pathogenicity* / Q000502:physiology
chemical_list: D017361:Viral Nonstructural Proteins; C531936:nonstructural protein 1, West Nile virus