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

To test whether rAAV-N796 could protect mice from RAbV infection in the masseter muscle, as shown in Fig. 3b , the mice were intramuscularly treated with rAAV-N796 and then intramuscularly challenged with a lethal dose (20 LD 50 ) of RAbV CVS-11 48 hr later. The results showed that there was partial protection (37.5 ± 3.7%) against virulent RAbV challenge in mice pretreated with rAAV-N796 and no protection in mice pretreated with rAAV-Neg. To check whether intracerebral inoculation with rAAV-N796 could protect mice from intramuscular infection with RAbV, as shown in Fig. 3C , the mice were first intracerebrally treated with rAAV-N796 and were then intramuscularly challenged with a lethal dose (20 LD 50 ) of RAbV CVS-11 48 hr later. Treatment of mice with rAAV-N796 demonstrated 62.5 ± 4.7% protection, and all the mice treated with rAAV-Neg died at 21 days post-challenge. The mice that survived did not develop symptoms and remained healthy for the entire period of experimentation. Moreover, at 6 days post challenge, we checked the N gene mRNA level in the brain for the three administrations. The results showed (Fig. 3E) that N gene mRNA level in the rAAV-N796-treated mice brain was significantly decreased. Also, the N gene mRNA level in the intracerebral pretreatment group was lower than that in the intramuscular pretreatment group, which agreed with the result pertaining to mouse survival rate.