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Functional characterization of new allelic polymorphisms identified in the promoter region of the human M x A gene
Author(s) -
Tran Thi Duc T.,
Desmecht D.,
Cornet A.
Publication year - 2013
Publication title -
international journal of immunogenetics
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.41
H-Index - 47
eISSN - 1744-313X
pISSN - 1744-3121
DOI - 10.1111/j.1744-313x.2012.01153.x
Subject(s) - biology , gene , allele , promoter , genetics , gene isoform , innate immune system , effector , transcription (linguistics) , rna , gene expression , reporter gene , microbiology and biotechnology , immune system , linguistics , philosophy
Summary The M x proteins are high‐molecular‐weight dynamin‐like proteins whose expression depends strictly on type‐ I and type‐ III interferons ( IFN ). Some isoforms are able to inhibit the life cycle of one or several viruses and are thus components of innate immune response. The human M x A protein displays the broadest antiviral spectrum which makes it appear as a key antiviral effector of innate immunity. Allelic polymorphisms located in the M x A gene promoter can be expected to affect the magnitude of M x A m RNA transcription in response to IFN s and therefore to alter the severity of viral diseases in humans. Here, three single nucleotide polymorphism sites (−309, −101 and +20) were examined for their ability to alter M x A gene promoter‐driven reporter expression. We show that, besides the previously reported role of −123 A and −88 T , the presence of ‐101 G is equally important. Moreover, when a promoter construct carries these three critical nucleotides, a first additional positive effect is conferred by a C at position −309 and, in this latter case, a second additional effect is produced by a A at position +20. This finding is clinically useful to improve prediction of IFN ‐responsiveness in patients not only with viral diseases for which type‐ I IFN therapy is used.