title: Bovine foamy virus transactivator BTas interacts with cellular RelB to enhance viral transcription.
abstract: Viruses are obligate intracellular parasites that depend on cellular machinery for their efficient transcription and replication. In a previous study we reported that bovine foamy virus (BFV) is able to activate the nuclear factor κB (NF-κB) pathway through the action of its transactivator BTas to enhance viral transcription. However, the mechanism used by NF-κB to enhance BFV transcription remains elusive. To address this question, we employed a yeast two-hybrid assay to screen for BTas-interacting proteins. We found that RelB, a member of NF-κB protein family, interacts with BTas. We confirmed the putative RelB-BTas interaction in vitro and in vivo and identified the protein regions responsible for the RelB-BTas interaction. Using a luciferase reporter assay, we next showed that RelB enhances BFV transcription (BTas-induced long terminal repeat [LTR] transactivation) and that this process requires both the localization of the RelB-BTas interaction in the nucleus and the Rel homology domain of RelB. The knockdown of the cellular endogenous RelB protein using small interfering RNA (siRNA) significantly attenuated BTas-induced LTR transcription. The results of chromatin immunoprecipitation (ChIP) analysis showed that endogenous RelB binds to the viral LTR in BFV-infected cells. Together, these results suggest that BFV engages the RelB protein as a cotransactivator of BTas to enhance viral transcription. In addition, our findings indicate that BFV infection upregulates cellular RelB expression through BTas-induced NF-κB activation. Thus, this study demonstrates the existence of a positive-feedback circuit in which BFV utilizes the host's NF-κB pathway through the RelB protein for efficient viral transcription.
authors.affiliation: Nankai University, Tianjin 300071, China.
authors.forename: Jian
authors.initials: J
authors.lastname: Wang
authors.forename: Juan
authors.initials: J
authors.lastname: Tan
authors.forename: Hongyan
authors.initials: H
authors.lastname: Guo
authors.forename: Qicheng
authors.initials: Q
authors.lastname: Zhang
authors.forename: Rui
authors.initials: R
authors.lastname: Jia
authors.forename: Xuan
authors.initials: X
authors.lastname: Xu
authors.forename: Yunqi
authors.initials: Y
authors.lastname: Geng
authors.forename: Wentao
authors.initials: W
authors.lastname: Qiao
mesh_terms: D000818:Animals; D002417:Cattle; D002418:Cattle Diseases / Q000378:metabolism* / Q000821:virology; D002460:Cell Line; D015967:Gene Expression Regulation, Viral; D006801:Humans; D011485:Protein Binding; D012192:Retroviridae Infections / Q000378:metabolism* / Q000821:virology*; D016092:Spumavirus / Q000235:genetics / Q000378:metabolism*; D015534:Trans-Activators / Q000235:genetics / Q000378:metabolism*; D051841:Transcription Factor RelB / Q000235:genetics / Q000378:metabolism*; D014158:Transcription, Genetic; D014764:Viral Proteins / Q000235:genetics / Q000378:metabolism*
chemical_list: D015534:Trans-Activators; D014764:Viral Proteins; D051841:Transcription Factor RelB