CHIA-CHI KUChe, Xi-BingXi-BingCheReichelt, MikeMikeReicheltRajamani, JayaJayaRajamaniSchaap-Nutt, AnneAnneSchaap-NuttHuang, Ke-JungKe-JungHuangSommer, Marvin HMarvin HSommerChen, Yi-ShunYi-ShunChenChen, Yi-YuanYi-YuanChenArvin, Ann MAnn MArvin2019-07-182019-07-182011-0208189641https://www.scopus.com/inward/record.uri?eid=2-s2.0-79951947294&doi=10.1038%2ficb.2010.83&partnerID=40&md5=a8a8499e55331bd495e7a0de34c5fc9ehttps://scholars.lib.ntu.edu.tw/handle/123456789/414242MxA 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.enherpes simplex virus-1 | IFN-α/β | immune evasion | mRNA alternative splicing[SDGs]SDG3journal article10.1038/icb.2010.83206036362-s2.0-79951947294WOS:000287445400005https://api.elsevier.com/content/abstract/scopus_id/79951947294