{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,8]],"date-time":"2026-10-08T21:31:39Z","timestamp":1791495099376,"version":"4.3.4"},"reference-count":35,"publisher":"American Society for Microbiology","issue":"6","license":[{"start":{"date-parts":[[2012,3,15]],"date-time":"2012-03-15T00:00:00Z","timestamp":1331769600000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/journals.asm.org\/non-commercial-tdm-license"}],"content-domain":{"domain":["journals.asm.org"],"crossmark-restriction":true},"short-container-title":["J Virol"],"published-print":{"date-parts":[[2012,3,15]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n          <jats:p>Mitogen-activated protein kinases (MAPKs) are a family of serine-threonine protein kinases involved in many cellular processes, including cell proliferation, differentiation, inflammation, and cell death. Activation of several MAPKs, including extracellular signal-regulated kinase 1 and 2 (ERK1\/2), p38, and c-Jun N-terminal kinase (JNK), results in stimulation of activator protein 1 (AP-1), which promotes gene transcription. Previous studies have demonstrated that varicella-zoster virus (VZV) infection activates ERK1\/2, p38, and JNK to promote viral replication, but the underlying mechanism(s) is unclear. To identify viral proteins responsible for the activation of MAPK, we used a proteomic approach to screen viral proteins for AP-1 promoter activation by an AP-1\u2013luciferase reporter assay. We found that VZV ORF12 protein, located in the tegument of virions, enhances AP-1 reporter activity. This effect of ORF12 protein was markedly inhibited by a MAPK\/ERK kinase 1 and 2 (MEK1\/2) inhibitor (U0126), partially blocked by a p38 inhibitor (SB202190), but not inhibited by a JNK inhibitor (SP600125). Expression of VZV ORF12 protein in cells resulted in phosphorylation of ERK1\/2 and p38 but not JNK. Infection of cells with a VZV ORF12 deletion mutant resulted in reduced levels of phosphorylated ERK1\/2 (p-ERK1\/2) compared to infection with wild-type VZV. Furthermore, deletion of ORF12 rendered VZV-infected cells more susceptible to staurosporine-induced apoptosis. In conclusion, VZV ORF12 protein activates the AP-1 pathway by selectively triggering the phosphorylation of ERK1\/2 and p38. Cells infected with a VZV ORF12 deletion mutant have reduced levels of p-ERK1\/2 and are more susceptible to apoptosis than cells infected with wild-type VZV.<\/jats:p>","DOI":"10.1128\/jvi.06923-11","type":"journal-article","created":{"date-parts":[[2012,1,12]],"date-time":"2012-01-12T04:56:00Z","timestamp":1326344160000},"page":"3143-3151","update-policy":"https:\/\/doi.org\/10.1128\/asmj-crossmark-policy-page","source":"Crossref","is-referenced-by-count":55,"title":["Varicella-Zoster Virus ORF12 Protein Triggers Phosphorylation of ERK1\/2 and Inhibits Apoptosis"],"prefix":"10.1128","volume":"86","author":[{"given":"XueQiao","family":"Liu","sequence":"first","affiliation":[{"name":"Medical Virology Section, Laboratory of Infectious Diseases, National Institutes of Health, Bethesda, Maryland, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Qingxue","family":"Li","sequence":"additional","affiliation":[{"name":"Medical Virology Section, Laboratory of Infectious 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