Adeno-Associated Viruses Serotype 2-Mediated RNA Interference Efficiently Inhibit Rabies Virus Replication In Vitro and Vivo
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概要
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To investigate the potential of adeno-associated viruses serotype 2 (AAV2)-mediated RNA interference (RNAi) as antiviral agent against rabies, a recombinant AAV2 vectors expressing siRNA targeting nucleoprotein (N) gene of rabies virus (RABV) (rAAV-N796) were constructed and evaluated. When NA cells pretreated with rAAV-N796 were challenged with RABV, there was 37.8 ± 3.4 to 55.1 ± 5.3% reduction in RABV virus titer. When cells pre-challenged with RABV were treated with rAAV-N796, there was 4.4 ± 1.4 to 28.8 ± 3.2% reduction in RABV virus titer. Relative quantification of RABV transcripts using real-time PCR and western blot revealed that the knockdown of RABV-N gene transcripts was based on the rAAV-N796 inoculation titer. Whatever NA cells was treated with rAAV-N796 before or after challenged with RABV, significant reduction was observed in both administrations. When mice treated intracerebrally with rAAV-N796 were challenged intracerebrally or intramuscally with lethal RABV, there was 50 ± 5.3 and 62.5 ± 4.7% protection, respectively. When mice treated intramuscally with rAAV-N796 were challenged intramuscally with lethal RABV, there was 37.5 ± 3.7% protection. When mice were intracerebrally and intramuscally with rAAV-N796 after exposed to RABV infection 24 hr later, there was 25 ± 4.1% protection The N gene mRNA level in challenged mice brain from three different administrations was reduced with 55, 68, 32 and 25%, respectively. These results indicated that AAV2 vector-mediated siRNA delivery in vitro in NA cells inhibited RABV multiplication; in vivo inhibited RABV multiplication in mice brain and imparted partial protection against lethal rabies. So it may have a potential to be used as an alternative antiviral approach against rabies.
著者
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YANG Song-Tao
Military Veterinary Institute, Academy of Military Medical Sciences, 666 Liuyin Road, Changchun 130122, Jilin Province, China
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GUO Xiao-Feng
College of Veterinary Medicine, South China Agricultural University, 483 Wushan Road, Guangzhou 510642, P. R. China
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XIA Xian-Zhu
Military Veterinary Institute, Academy of Military Medical Sciences, 666 Liuyin Road, Changchun 130122, Jilin Province, China
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GAO Yu-Wei
Military Veterinary Institute, Academy of Military Medical Sciences, 666 Liuyin Road, Changchun 130122, Jilin Province, China
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ZHAO Yong-Kun
Military Veterinary Institute, Academy of Military Medical Sciences, 666 Liuyin Road, Changchun 130122, Jilin Province, China
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WANG Tie-Cheng
Military Veterinary Institute, Academy of Military Medical Sciences, 666 Liuyin Road, Changchun 130122, Jilin Province, China
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WU Hong-Xia
College of Veterinary Medicine, South China Agricultural University, 483 Wushan Road, Guangzhou 510642, P. R. China
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WANG Hua-Lei
Military Veterinary Institute, Academy of Military Medical Sciences, 666 Liuyin Road, Changchun 130122, Jilin Province, China
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YANG Yu-Jiao
Military Veterinary Institute, Academy of Military Medical Sciences, 666 Liuyin Road, Changchun 130122, Jilin Province, China
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MA Jin-Zhu
Military Veterinary Institute, Academy of Military Medical Sciences, 666 Liuyin Road, Changchun 130122, Jilin Province, China
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WU Hone-Xia
College of Veterinary Medicine, South China Agricultural University, 483 Wushan Road, Guangzhou 510642, P. R. China