Single nucleotide polymorphisms in genes for 2'-5'-oligoadenylate synthetase and RNase L inpatients hospitalized with West Nile virus infection.

TitleSingle nucleotide polymorphisms in genes for 2'-5'-oligoadenylate synthetase and RNase L inpatients hospitalized with West Nile virus infection.
Publication TypeJournal Article
Year of Publication2005
AuthorsYakub, I, Lillibridge, KM, Moran, A, Gonzalez, OY, Belmont, J, Gibbs, RA, Tweardy, DJ
JournalJ Infect Dis
Volume192
Issue10
Pagination1741-8
Date Published2005 Nov 15
ISSN0022-1899
Keywords2',5'-Oligoadenylate Synthetase, Adult, Aged, Endoribonucleases, Exons, Female, Genetic Predisposition to Disease, Hospitalization, Humans, Male, Middle Aged, Polymorphism, Single Nucleotide, Sequence Analysis, DNA, West Nile Fever, West Nile virus
Abstract

BACKGROUND: Infection with the flavivirus West Nile virus (WNV) is a growing problem across the United States, where there is a case-fatality rate of 15%-29% in individuals >70 years old and no consistently effective treatment. Susceptibility to WNV disease in inbred strains of mice was mapped to a nonsense mutation in the gene encoding the 1b isoform of 2'-5'-oligoadenylate synthetase (OAS), a member of the OAS/RNase L system of innate viral resistance. Genetic susceptibility to severe WNV disease in humans has not been determined.METHODS: We sequenced each exon within all OAS and RNASEL genes in 33 individuals hospitalized with WNV infection in Houston to assess if there is a defect in this system in patients with severe WNV disease.RESULTS: Sequencing did not reveal any insertions, deletions, or nonsense mutations in any OAS or RNASEL gene. However, comparison of the exonic sequences between case patients and control subjects identified 23 single nucleotide polymorphisms (SNPs), including a synonymous SNP in OASL exon 2 (rs3213545), in which the reference allele occurred at a higher frequency in case patients (P < .004).CONCLUSION: Because the reference allele contains a splice enhancer site, our finding suggests that the RNA transcripts generated from this allele may undergo increased splicing, which results in a dominant-negative OASL isozyme similar to the nonsense/truncation mutant form of Oas1b in mice.

DOI10.1086/497340
Alternate JournalJ. Infect. Dis.
PubMed ID16235172