Rabies viruses leader RNA interacts with host Hsc70 and inhibits virus replication
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Ran Zhang1,2, Chuangang Liu1,2, Yunzi Cao1,2, Muhammad Jamal1,2, Xi Chen1,2, Jinfang Zheng5, Liang Li1,2, Jing You1,2, Qi Zhu1,2, Shiyong Liu5, Jinxia Dai1,2, Min Cui1,2, Zhen F. Fu1,2,4 and Gang Cao1,2,3
1State Key Laboratory of Agricultural Microbiology, Huazhong Agricultural University, Wuhan 430070, China
2College of Veterinary Medicine, Huazhong Agricultural University, Wuhan 430070, China
3Key Laboratory of Development of Veterinary Diagnostic Products, Ministry of Agriculture, College of Veterinary Medicine, Huazhong Agricultural University, Wuhan 430070, China
4Department of Pathology, College of Veterinary Medicine, University of Georgia, Athens, GA 30602, USA
5Department of Physics and Key Laboratory of Molecular Biophysics of the Ministry of Education, Huazhong University of Science and Technology, Wuhan 430074, China
Gang Cao, email: [email protected]
Zhen F. Fu, email: [email protected]
Keywords: leader RNA (LeRNA), rabies virus (RABV), Hsc70, post-exposure prophylaxis (PEP), RNA-Protein interaction
Received: May 09, 2016 Accepted: March 13, 2017 Published: March 23, 2017
Viruses have been shown to be equipped with regulatory RNAs to evade host defense system. It has long been known that rabies virus (RABV) transcribes a small regulatory RNA, leader RNA (leRNA), which mediates the transition from viral RNA transcription to replication. However, the detailed molecular mechanism remains enigmatic. In the present study, we determined the genetic architecture of RABV leRNA and demonstrated its inhibitory effect on replication of wild-type rabies, DRV-AH08. The RNA immunoprecipitation results suggest that leRNA inhibits RABV replication via interfering the binding of RABV nucleoprotein with genomic RNA. Furthermore, we identified heat shock cognate 70 kDa protein (Hsc70) as a leRNA host cellular interacting protein, of which the expression level was dynamically regulated by RABV infection. Notably, our data suggest that Hsc70 was involved in suppressing RABV replication by leader RNA. Finally, our experiments imply that leRNA might be potentially useful as a novel drug in rabies post-exposure prophylaxis. Together, this study suggested leRNA in concert with its host interacting protein Hsc70, dynamically down-regulate RABV replication.
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