title: Positional cloning of the murine flavivirus resistance gene.
abstract: Inbred mouse strains exhibit significant differences in their susceptibility to viruses in the genus Flavivirus, which includes human pathogens such as yellow fever, Dengue, and West Nile virus. A single gene, designated Flv, confers this differential susceptibility and was mapped previously to a region of mouse chromosome 5. A positional cloning strategy was used to identify 22 genes from the Flv gene interval including 10 members of the 2'-5'-oligoadenylate synthetase gene family. One 2'-5'-oligoadenylate synthetase gene, Oas1b, was identified as Flv by correlation between genotype and phenotype in nine mouse strains. Susceptible mouse strains produce a protein lacking 30% of the C-terminal sequence as compared with the resistant counterpart because of the presence of a premature stop codon. The Oas1b gene differs from all the other murine Oas genes by a unique four-amino acid deletion in the P-loop located within the conserved RNA binding domain. Expression of the resistant allele of Oas1b in susceptible embryo fibroblasts resulted in partial inhibition of the replication of a flavivirus but not of an alpha togavirus.
authors.affiliation: Department of Biology, Georgia State University, Atlanta, GA 30303, USA.
authors.forename: Andrey A
authors.initials: AA
authors.lastname: Perelygin
authors.forename: Svetlana V
authors.initials: SV
authors.lastname: Scherbik
authors.forename: Igor B
authors.initials: IB
authors.lastname: Zhulin
authors.forename: Bronislava M
authors.initials: BM
authors.lastname: Stockman
authors.forename: Yan
authors.initials: Y
authors.lastname: Li
authors.forename: Margo A
authors.initials: MA
authors.lastname: Brinton
mesh_terms: D015088:2',5'-Oligoadenylate Synthetase / Q000235:genetics; D000818:Animals; D002460:Cell Line; D002874:Chromosome Mapping; D003001:Cloning, Molecular; D006224:Cricetinae; D005260:Female; D005416:Flavivirus / Q000472:pathogenicity* / Q000502:physiology; D018177:Flavivirus Infections / Q000235:genetics*; D015870:Gene Expression; D006801:Humans; D008297:Male; D051379:Mice; D008815:Mice, Inbred Strains; D008969:Molecular Sequence Data; D010802:Phylogeny; D011247:Pregnancy; D014018:Tissue Distribution; D014779:Virus Replication
chemical_list: D015088:2',5'-Oligoadenylate Synthetase