牛泡沫病毒BBet抑制BTas反式激活功能负调控病毒复制  

Bovine Foamy Virus BBet Inhibits BTas Trans-Activation and Negative Control of Viral Replication

作　　者：崔金刚 拜晓勃 张其程[1] 邵鹏 谈娟[1] 乔文涛[1] Cui Jingang;Bai Xiaobo;Zhang Qicheng;Shao Peng;Tan Juan;Qiao Wentao(Key laboratory of Molecular Microbiology and Biotechnology,Ministry of Education,College of Life Sciences,Nankai University,Tianjin 300071,China)

机构地区：[1]南开大学生命科学学院,分子微生物与技术教育部重点实验室,天津300071

出　　处：《南开大学学报（自然科学版）》2024年第1期45-49,共5页Acta Scientiarum Naturalium Universitatis Nankaiensis

基　　金：国家自然科学基金(81571988,31670151)。

摘　　要：泡沫病毒(foamy virus,FV)属于反转录病毒科中的泡沫病毒亚科、泡沫病毒属.其基因组除编码结构蛋白Gag、Pol及Env外,同时还编码2个非结构蛋白Tas和Bet.Tas是泡沫病毒的正调控蛋白,通过结合在病毒启动子上游的DNA调控元件上正调控病毒基因表达.Bet对病毒复制具有一定的负调控作用,但作用机制尚无报道.利用实验室筛选得到的牛泡沫病毒(bovine fomay virus,BFV)3026可释放株(BFV-Z1),采用不同感染复数(0.01及0.1)感染BFV Bet(BBet)稳定表达细胞系及对照细胞系,分析传代后病毒滴度,确证BBet抑制BFV复制;分析BBet对病毒启动子活性的影响,发现Bet对BFV的2个启动子LTR和IP本底活性影响较小,但BBet可抑制BFV Tas(BTas)对BFV的LTR和IP启动子的反式激活.进一步机制分析发现BBet未显著影响BTas的细胞定位,也不能直接结合启动子上游BTas相关应答序列,推测BBet可能通过抑制BTas结合启动子应答元件之后的分子事件,如募集转录复合物等过程负调控病毒复制.Foamy virus belongs to the foam virus subfamily of the family Retroviridae and belongs to the genus foamy virus.Its genome,in addition to the encoded structural proteins Gag,Pol and Env,encodes two non-structural proteins,Tas and Bet.Tas is a positive regulatory protein of foamy virus,which regulates the expression of viral gene by binding to the DNA regulatory element upstream of the viral promoter.Bet has a certain negative regulation effect on viral replication,but the mechanism of action has not been reported.Bovine fomay virus(BFV) 3026 releasable strain(BFV-Z1) was obtained by laboratory screening,and BFV Bet(BBet) stably expressing cell lines and control cell lines were infected with different multiplicity of infection(0.01 and 0.1).The virus titer after passage was analyzed to confirm that BBet inhibited BFV replication;The effect of Bet on the activity of the viral promoter was analyzed,and it was found that the Bet had little effect on the LTR and IP background activity of the BFV promoter,but the BBet can inhibit the trans-activation of the LTR and the IP promoter of the BTas to the BFV.The further mechanism analysis found that the BBet did not significantly affect the cell localization of the BTas,nor did it interfere with the BTas binding-related promoter-response element,suggesting that the BBet was negatively regulating viral replication by inhibiting the molecular events following the BTas binding to the promoter-response element,such as the recruitment of a transcription complex.

关 键 词：牛泡沫病毒 BBet BTas 

分 类 号：R373.3[医药卫生—病原生物学]