Journal
IMMUNOLOGY AND CELL BIOLOGY
Volume 89, Issue 2, Pages 173-182Publisher
WILEY
DOI: 10.1038/icb.2010.83
Keywords
herpes simplex virus-1; IFN-alpha/beta; immune evasion; mRNA alternative splicing
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Funding
- NIH [AI20459, AI053846]
- National Science Council, Taiwan [NSC97-2320-B-002-005-MY3]
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MxA is an antiviral protein induced by interferon (IFN)-alpha/beta that is known to inhibit the replication of many RNA viruses. In these experiments, the 76-kDa MxA protein expressed in IFN-alpha-treated cells was shown to have antiviral activity against herpes simplex virus-1 (HSV-1), a human DNA virus. However, MxA was expressed as a 56-kDa protein in HSV-1-infected cells in the absence of IFN-alpha. This previously unrecognized MxA isoform was produced from an alternatively spliced MxA transcript that had a deletion of Exons 14-16 and a frame shift altering the C-terminus. The variant MxA (varMxA) isoform was associated with HSV-1 regulatory proteins and virions in nuclear replication compartments. varMxA expression enhanced HSV-1 infection as shown by a reduction in infectious virus titers from cells in which MxA had been inhibited by RNA interference and by an increase in HSV-1 titers when the 56-kDa varMxA was expressed constitutively. Thus, the human MxA gene encodes two MxA isoforms, which are expressed differentially depending on whether the stimulus is IFN-alpha or HSV-1. These findings show that alternative splicing of cellular mRNA can result in expression of a novel isoform of a host defense gene that supports instead of restricting viral infection. Immunology and Cell Biology (2011) 89, 173-182; doi:10.1038/icb.2010.83; published online 6 July 2010
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