Significance of the Myxovirus resistance A (MxA) gene - 123C>A single-nucleotide polymorphism in suppressed interferon ß induction of severe acute respiratory syndrome coronavirus infection

Abstract

Myxovirus resistance A (MxA) is an antiviral protein induced by interferon a and ß (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-α 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. © 2010 by the Infectious Diseases Society of America. All rights reserved.