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Oncotarget. 2017 Jul 4;8(27):43822-43837. doi: 10.18632/oncotarget.16517.

Rabies viruses leader RNA interacts with host Hsc70 and inhibits virus replication.

Zhang R1,2, Liu C1,2, Cao Y1,2, Jamal M1,2, Chen X1,2, Zheng J3, Li L1,2, You J1,2, Zhu Q1,2, Liu S3, Dai J1,2, Cui M1,2, Fu ZF1,2,4, Cao G1,2,5.

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State Key Laboratory of Agricultural Microbiology, Huazhong Agricultural University, Wuhan 430070, China.
College of Veterinary Medicine, Huazhong Agricultural University, Wuhan 430070, China.
Department of Physics and Key Laboratory of Molecular Biophysics of the Ministry of Education, Huazhong University of Science and Technology, Wuhan 430074, China.
Department of Pathology, College of Veterinary Medicine, University of Georgia, Athens, GA 30602, USA.
Key Laboratory of Development of Veterinary Diagnostic Products, Ministry of Agriculture, College of Veterinary Medicine, Huazhong Agricultural University, Wuhan 430070, China.


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.


Hsc70; RNA-Protein interaction; leader RNA (LeRNA); post-exposure prophylaxis (PEP); rabies virus (RABV)

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