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Herpes simplex virus‐1 induces expression of a novel MxA isoform that enhances viral replication
Author(s) -
Ku ChiaChi,
Che XiBing,
Reichelt Mike,
Rajamani Jaya,
SchaapNutt Anne,
Huang KeJung,
Sommer Marvin H,
Chen YiShun,
Chen YiYuan,
Arvin Ann M
Publication year - 2011
Publication title -
immunology and cell biology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.999
H-Index - 104
eISSN - 1440-1711
pISSN - 0818-9641
DOI - 10.1038/icb.2010.83
Subject(s) - biology , herpes simplex virus , gene isoform , viral replication , interferon , gene , virology , virus , rna , alternative splicing , gene expression , exon , rna interference , antiviral protein , microbiology and biotechnology , genetics
MxA is an antiviral protein induced by interferon (IFN)‐α/β that is known to inhibit the replication of many RNA viruses. In these experiments, the 76‐kDa MxA protein expressed in IFN‐α‐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‐α. 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‐α 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.