title: Unconventional sequence requirement for viral late gene core promoters of murine gammaherpesvirus 68.
abstract: Infection with the human gammaherpesviruses, Epstein-Barr virus (EBV) and Kaposi's sarcoma-associated herpesvirus (KSHV), is associated with several cancers. During lytic replication of herpesviruses, viral genes are expressed in an ordered cascade. However, the mechanism by which late gene expression is regulated has not been well characterized in gammaherpesviruses. In this study, we have investigated the cis element that mediates late gene expression during de novo lytic infection with murine gammaherpesvirus 68 (MHV-68). A reporter system was established and used to assess the activity of viral late gene promoters upon infection with MHV-68. It was found that the viral origin of lytic replication, orilyt, must be on the reporter plasmid to support activation of the late gene promoter. Furthermore, the DNA sequence required for the activation of late gene promoters was mapped to a core element containing a distinct TATT box and its neighboring sequences. The critical nucleotides of the TATT box region were determined by systematic mutagenesis in the reporter system, and the significance of these nucleotides was confirmed in the context of the viral genome. In addition, EBV and KSHV late gene core promoters could be activated by MHV-68 lytic replication, indicating that the mechanisms controlling late gene expression are conserved among gammaherpesviruses. Therefore, our results on MHV-68 establish a solid foundation for mechanistic studies of late gene regulation.
authors.affiliation: Department of Molecular & Medical Pharmacology,University of California at Los Angeles, Los Angeles, California, USA.
authors.forename: Elaine
authors.initials: E
authors.lastname: Wong-Ho
authors.forename: Ting-Ting
authors.initials: TT
authors.lastname: Wu
authors.forename: Zoe H
authors.initials: ZH
authors.lastname: Davis
authors.forename: Bingqing
authors.initials: B
authors.lastname: Zhang
authors.forename: Jian
authors.initials: J
authors.lastname: Huang
authors.forename: Hao
authors.initials: H
authors.lastname: Gong
authors.forename: Hongyu
authors.initials: H
authors.lastname: Deng
authors.forename: Fenyong
authors.initials: F
authors.lastname: Liu
authors.forename: Britt
authors.initials: B
authors.lastname: Glaunsinger
authors.forename: Ren
authors.initials: R
authors.lastname: Sun
mesh_terms: D000818:Animals; D001483:Base Sequence; D015967:Gene Expression Regulation, Viral; D006566:Herpesviridae Infections / Q000662:veterinary* / Q000821:virology; D051379:Mice; D008969:Molecular Sequence Data; D011401:Promoter Regions, Genetic; D018741:Replication Origin; D018144:Rhadinovirus / Q000235:genetics* / Q000502:physiology; D012376:Rodent Diseases / Q000821:virology*; D016385:TATA Box; D014158:Transcription, Genetic; D014764:Viral Proteins / Q000235:genetics* / Q000378:metabolism; D014779:Virus Replication
chemical_list: D014764:Viral Proteins