title: Herpes simplex virus type 1 infection activates the Epstein-Barr virus replicative cycle via a CREB-dependent mechanism.
abstract: The reactivation of latent Epstein-Barr virus (EBV) to lytic replication is important in pathogenesis and requires virus-host cellular interactions. However, the mechanism underlying the reactivation of EBV is not yet fully understood. In the present study, herpes simplex virus type 1 (HSV-1) was shown to induce the reactivation of latent EBV by triggering BZLF1 expression. The BZLF1 promoter (Zp) was not activated by HSV-1 essential glycoprotein-induced membrane fusion. Nevertheless, Zp was activated within 6 h post HSV-1 infection in virus entry-dependent and replication-independent manners. Using a panel of Zp deletion mutants, HSV-1 was shown to promote Zp through a cyclic adenosine monophosphate (cAMP) response element (CRE) located in ZII. The phosphorylated cAMP response element-binding (phos-CREB) protein, the cellular transactivator that binds to CRE, also increased after HSV-1 infection. By transient transfection, cAMP-dependent protein kinase A and HSV-1 US3 protein were found to be capable of activating Zp in CREB- and CRE-dependent manners. The relationship between EBV activation and HSV-1 infection revealed a possible common mechanism that stimulated latent EBV into lytic cycles in vivo.
authors.affiliation: State Key Laboratory of Respiratory Disease, Guangzhou Institutes of Biomedicine and Health, Chinese Academy of Sciences, Guangzhou 510530, China.
authors.forename: Hongling
authors.initials: H
authors.lastname: Wu
authors.forename: Ting
authors.initials: T
authors.lastname: Li
authors.forename: Musheng
authors.initials: M
authors.lastname: Zeng
authors.forename: Tao
authors.initials: T
authors.lastname: Peng
mesh_terms: D017362:Cyclic AMP Response Element-Binding Protein / Q000235:genetics / Q000378:metabolism; D004267:DNA Viruses / Q000235:genetics / Q000378:metabolism; D015967:Gene Expression Regulation, Viral; D057809:HEK293 Cells; D018259:Herpesvirus 1, Human / Q000235:genetics / Q000378:metabolism / Q000472:pathogenicity* / Q000502:physiology; D004854:Herpesvirus 4, Human / Q000235:genetics / Q000378:metabolism / Q000472:pathogenicity* / Q000502:physiology; D054884:Host-Pathogen Interactions; D006801:Humans; D010766:Phosphorylation; D011401:Promoter Regions, Genetic; D011485:Protein Binding; D017346:Protein Serine-Threonine Kinases / Q000235:genetics / Q000378:metabolism; D017384:Sequence Deletion; D013997:Time Factors; D015534:Trans-Activators / Q000235:genetics / Q000378:metabolism; D014162:Transfection; D014764:Viral Proteins / Q000235:genetics / Q000378:metabolism; D014775:Virus Activation; D053586:Virus Internalization; D017735:Virus Latency
chemical_list: C063676:BZLF1 protein, Herpesvirus 4, Human; C115163:CREB1 protein, human; D017362:Cyclic AMP Response Element-Binding Protein; D015534:Trans-Activators; D014764:Viral Proteins; D017346:Protein Serine-Threonine Kinases; C095207:US3 protein, Human herpesvirus 1