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- Title
Significance of the Myxovirus Resistance A (MxA) Gene —123C>A Single-Nucleotide Polymorphism in Suppressed Interferon β Induction of Severe Acute Respiratory Syndrome Coronavirus Infection.
- Authors
Chi-Yun Ching, Johannes; Kelvin Yuen Kwong Chan; Eric Hing Leung Lee; Mei-Shu Xu; Campbell Kam Po Ting; So, Thomas M. K.; Sham, Pak C.; Leung, Gabriel M.; Peiris, Joseph S. M.; Ui-Soon Khoo
- Abstract
Myxovirus resistance A (MxA) is an antiviral protein induced by interferon a and β (IFN-α, IFN-β) that can inhibit viral replication. The minor alleles of the -88G>T and -123C>A MxA promoter single-nucleotide polymorphisms (SNPs) are associated with increased promoter activity and altered response to IFN-a and IFN-β treatment. Here, we demonstrate that the -123A minor allele provided stronger binding affinity to nuclear proteins extracted from IFN-β-untreated cells than did the wild-type allele, whereas the -88T allele showed preferential binding after IFN-β stimulation. Endogenous IFN-α and IFN-β induction can be suppressed in severe acute respiratory syndrome (SARS) coronavirus infection. In support of our in vitro findings, a large case-control genetic-association study for SARS coronavirus infection confirmed that the -123A minor-allele carriers were significantly associated with lower risk of SARS coronavirus infection, whereas the -88T minorallele carriers were insignificant after adjustment for confounding effects. This suggests that -123C>A plays a more important role in modulating basal MxA expression, thus contributing more significantly to innate immune response against viral infections that suppress endogenous IFN-α and IFN-β induction such as SARS coronavirus.
- Subjects
ORTHOMYXOVIRUSES; INTERFERONS; VIRAL replication; CORONAVIRUS diseases; SARS disease; GENE frequency; NUCLEAR proteins; PROTEIN binding; GENETIC polymorphisms
- Publication
Journal of Infectious Diseases, 2010, Vol 201, Issue 12, p1899
- ISSN
0022-1899
- Publication type
Article
- DOI
10.1086/652799