title: Activation and degradation of open reading frame 45 by the replication and transcription activator of Kaposi's sarcoma-associated herpesvirus.
abstract: The open reading frame 45 (ORF45) of the Kaposi's sarcoma-associated herpesvirus (KSHV) is an immediate-early phosphorylated tegument protein critical for viral escape from host immune surveillance. Its expression is upregulated by the viral replication and transcription activator (RTA), a key protein that controls the switch from latency to lytic replication. We report here that ORF45 expression was not only upregulated by RTA, but ORF45 could also be degraded by RTA in a proteasome-dependent manner. The ORF45 was activated by RTA via activation of the ORF45 promoter, and the promoter region from nt 69 271 to nt 69 026 was involved. In chronic KSHV infected TRE-BCBL-1 RTA cells, the endogenous ORF45 protein increased dramatically after the induction of RTA expression, but then decreased rapidly after 8 h post-induction. Our study suggests that RTA might control the kinetics of viral replication through fine-tuning of the level of ORF45 and other viral/host proteins.
authors.affiliation: 1TEDA Institute of Biological Sciences and Biotechnology, Nankai University, 23 Hongda Street, TEDA, Tianjin 300457, PR China 2Key Laboratory of Molecular Microbiology and Technology, Ministry of Education, 23 Hongda Street, TEDA, Tianjin 300457, PR China 3Tianjin Key Laboratory of Microbial Functional Genomics, 23 Hongda Street, TEDA, Tianjin 300457, PR China.
authors.forename: Ying
authors.initials: Y
authors.lastname: Wang
authors.affiliation: 1TEDA Institute of Biological Sciences and Biotechnology, Nankai University, 23 Hongda Street, TEDA, Tianjin 300457, PR China.
authors.forename: Kai
authors.initials: K
authors.lastname: Yu
authors.affiliation: 1TEDA Institute of Biological Sciences and Biotechnology, Nankai University, 23 Hongda Street, TEDA, Tianjin 300457, PR China.
authors.forename: Xiuzhi
authors.initials: X
authors.lastname: Pei
authors.affiliation: 1TEDA Institute of Biological Sciences and Biotechnology, Nankai University, 23 Hongda Street, TEDA, Tianjin 300457, PR China.
authors.forename: Tianzheng
authors.initials: T
authors.lastname: Zhang
authors.affiliation: 1TEDA Institute of Biological Sciences and Biotechnology, Nankai University, 23 Hongda Street, TEDA, Tianjin 300457, PR China.
authors.forename: Yuying
authors.initials: Y
authors.lastname: Guo
authors.affiliation: 4Nebraska Center for Virology and School of Biological Sciences, University of Nebraska, Lincoln, NE 68583, USA.
authors.forename: Charles
authors.initials: C
authors.lastname: Wood
authors.affiliation: 1TEDA Institute of Biological Sciences and Biotechnology, Nankai University, 23 Hongda Street, TEDA, Tianjin 300457, PR China 2Key Laboratory of Molecular Microbiology and Technology, Ministry of Education, 23 Hongda Street, TEDA, Tianjin 300457, PR China 3Tianjin Key Laboratory of Microbial Functional Genomics, 23 Hongda Street, TEDA, Tianjin 300457, PR China.
authors.forename: Jinzhong
authors.initials: J
authors.lastname: Wang
mesh_terms: D002460:Cell Line; D015967:Gene Expression Regulation, Viral; D019288:Herpesvirus 8, Human / Q000502:physiology*; D006801:Humans; D017874:Immediate-Early Proteins / Q000378:metabolism*; D046988:Proteasome Endopeptidase Complex / Q000378:metabolism; D059748:Proteolysis; D015534:Trans-Activators / Q000378:metabolism*; D014158:Transcription, Genetic
chemical_list: D017874:Immediate-Early Proteins; C456286:ORF45 protein, Kaposi's sarcoma-associated herpesvirus; C417604:Rta protein, Human herpesvirus 8; D015534:Trans-Activators; D046988:Proteasome Endopeptidase Complex