Functional characterization of new allelic polymorphisms identified in the promoter region of the human M x A gene

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.