Adeno-Associated Viruses Serotype 2-Mediated RNA Interference Efficiently Inhibits Rabies Virus Replication In Vitro and In Vivo

WU, Hong-Xia; WANG, Hua-Lei; GUO, Xiao-Feng; YANG, Yu-Jiao; MA, Jin-Zhu; WANG, Tie-Cheng; GAO, Yu-Wei; ZHAO, Yong-Kun; YANG, Song-Tao; XIA, Xian-Zhu

Clinical rabies, the CNS form of the disease, can be treated with anti-rabies RNAi through elimination of RAbV from the infected neurons by delivering anti-rabies siRNA effectively to the neurons [17] . rAAV2 has emerged as a vector of choice for gene transfer to the central nervous system [3] . So, in the in vivo experiment, the antiviral effect of intracerebral inoculation with rAAV-N796 (50 and 62% survival, respectively) was better than with intramuscular inoculation (38% survival). Whether the transduction efficiency in muscle is higher than in the brain needs to be investigated further. The survival rate of the intracerebral inoculation and infection group (50% survival) was lower than that of the intracerebral inoculation and intramuscular infection group (63% survival). After infection with RAbV, the time until symptoms were shown was associated with the site of infection. Once RAbV is introduced through the skin or mucous membrane, it replicates in the myocytes for hours or weeks and then migrates to nerves. If RAbV was introduced into the brain, it would replicate quickly. During the process of RAbV entry into brain from masseter muscle, rAAV-N796 has more time to transduce the neural cells and produce more siRNA than direct intracerebral infection. So, the antiviral effect of intracerebral inoculation and intramuscular infection was better than that of intracerebral inoculation and infection.