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

被引:28
作者
Ching, Johannes Chi-Yun [1 ]
Chan, Kelvin Yuen Kwong [1 ]
Lee, Eric Hing Leung [1 ]
Xu, Mei-Shu [1 ]
Ting, Campbell Kam Po [1 ]
So, Thomas M. K. [5 ]
Sham, Pak C. [2 ]
Leung, Gabriel M. [3 ]
Peiris, Joseph S. M. [4 ]
Khoo, Ui-Soon [1 ]
机构
[1] Univ Hong Kong, Dept Pathol, Hong Kong, Hong Kong, Peoples R China
[2] Univ Hong Kong, Dept Psychiat, Hong Kong, Hong Kong, Peoples R China
[3] Univ Hong Kong, Dept Community Med, Hong Kong, Hong Kong, Peoples R China
[4] Univ Hong Kong, Dept Microbiol, Hong Kong, Hong Kong, Peoples R China
[5] Princess Margaret Hosp, Dept Med & Geriatr, Hong Kong, Hong Kong, Peoples R China
关键词
EXPRESSING HUMAN MXA; HEPATITIS-C PATIENTS; GENE PROTECTS MICE; INFLUENZA-VIRUS; IN-VITRO; CONFERS RESISTANCE; SARS; PROMOTER; REPLICATION; INHIBITION;
D O I
10.1086/652799
中图分类号
R392 [医学免疫学]; Q939.91 [免疫学];
学科分类号
100102 ;
摘要
Myxovirus resistance A (MxA) is an antiviral protein induced by interferon alpha and beta (IFN-alpha, IFN-beta) 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-alpha and IFN-beta treatment. Here, we demonstrate that the -123A minor allele provided stronger binding affinity to nuclear proteins extracted from IFN-beta-untreated cells than did the wild-type allele, whereas the -88T allele showed preferential binding after IFN-beta stimulation. Endogenous IFN-alpha and IFN-beta 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 minor-allele 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-alpha and IFN-beta induction such as SARS coronavirus.
引用
收藏
页码:1899 / 1908
页数:10
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