title: HSV-1 stimulation-related protein HSRG1 inhibits viral gene transcriptional elongation by interacting with Cyclin T2.
abstract: The protein encoded by HSRG1 (HSV-1 stimulation-related gene 1) is a virally induced protein expressed in HSV-1-infected cells. We have already reported that HSRG1 is capable of interacting with transcriptional regulator proteins. To further analyze the effects of HSRG1 on the regulation of viral gene transcription, we expressed the HSRG1 protein in transfected cells and found that it postpones the proliferation of HSV-1. CAT (chloramphenicol acetyltransferase) assays also revealed that HSRG1 reduces transcription from HSV-1 promoters. Yeast two-hybrid and immunoprecipitation assays indicated that HSRG1 interacts with Cyclin T2, the regulatory subunit of P-TEFb, which is required for transcription elongation by RNA Pol II (RNAP II), and that amino acid residues 1-420 in Cyclin T2 are important for binding with HSRG1. Fluorescence assays suggested that the cellular localizations of those two proteins are influenced by their interaction. Further analyses with CAT assays revealed that HSRG1 inhibits the transcriptional activation by Cyclin T2 of viral promoters. Our results suggested that the inhibitory effects of HSRG1 on viral replication and proliferation are probably induced by its binding to Cyclin T2. Therefore, it is likely that HSRG1 inhibits viral gene transcriptional elongation by interacting with Cyclin T2.
authors.affiliation: Department of Viral Immunology, Institute of Medical Biology, Chinese Academy of Medical Sciences and Peking Union Medical College, Kunming 650118, China.
authors.forename: Wenjuan
authors.initials: W
authors.lastname: Wu
authors.forename: Xian
authors.initials: X
authors.lastname: Yu
authors.forename: Weizhong
authors.initials: W
authors.lastname: Li
authors.forename: Lei
authors.initials: L
authors.lastname: Guo
authors.forename: Longding
authors.initials: L
authors.lastname: Liu
authors.forename: Lichun
authors.initials: L
authors.lastname: Wang
authors.forename: Qihan
authors.initials: Q
authors.lastname: Li
mesh_terms: D000818:Animals; D016466:CHO Cells; D002522:Chlorocebus aethiops; D006224:Cricetinae; D003412:Cricetulus; D056906:Cyclin T / Q000235:genetics / Q000378:metabolism*; D015967:Gene Expression Regulation, Viral; D005814:Genes, Viral; D018259:Herpesvirus 1, Human / Q000502:physiology*; D006801:Humans; D047908:Intracellular Signaling Peptides and Proteins; D011401:Promoter Regions, Genetic; D011506:Proteins / Q000235:genetics / Q000378:metabolism*; D014158:Transcription, Genetic; D020798:Two-Hybrid System Techniques; D014709:Vero Cells; D014779:Virus Replication
chemical_list: D056906:Cyclin T; D047908:Intracellular Signaling Peptides and Proteins; C477373:MON1B protein, human; D011506:Proteins