Pathogenicity and protection in mice of rearranging the M gene of RABV HEP-Flury
MEI Ming-zhu1,2, YANG Xian-feng2, LONG Teng2, ZHANG Qiong2, ZHAO Jing2, TIAN Qin2, PENG Jiao-jiao2, LUO Jun2, JIANG He2, LIN Ying-yi2, LIN Zhi-xiong1, GUO Xiao-feng2
1.Guangzhou Custom Technology Center, Guangzhou 510623, China; 2.College of Veterinary Medicine, South China Agricultural University, Guangzhou 510642, China
Abstract:In order to help rabies vaccine candidate construction, the lethality and immunological protection between rHEP-Flury and M gene rearranged viruses were compared and analyzed. Lethality in suckling mice was performed by intracranial inoculating rHEP-Flury or M gene rearranged viruses, then LD50 was calculated. Protection of mice was performed by immunized once intramuscularly with different doses of rHEP-Flury or M gene rearranged viruses, then mice were challenged IC with CVS-24 and survivor numbers were evaluated. At the same time, the antibody level was assessed by ELISA. The lethality in suckling mice increased as the M gene was moved successively away from promoter proximal position to successive positions down the viral genome, that is M2<rHEP-Flury<M4. Protection of mice showed that the percent survival at the dose of 104 and 105FFU has no significant difference, however, at the dose of 103FFU, the percent survival of M gene rearranged viruses was clearly higher than that of rHEP-Flury. M gene rearrangement of HEP-Flury could decrease the viral lethality and increase the protection, which is benefit for the choose of rabies vaccine candidate.
梅明珠,杨先锋,龙腾,张琼,赵静,田钦,彭娇娇,罗均,姜贺,林颖仪,林志雄,郭霄峰. 狂犬病病毒HEP-Flury M基因重排在小鼠致病性和保护性研究[J]. 中国人兽共患病学报, 2020, 36(3): 173-177.
MEI Ming-zhu, YANG Xian-feng, LONG Teng, ZHANG Qiong, ZHAO Jing, TIAN Qin, PENG Jiao-jiao, LUO Jun, JIANG He, LIN Ying-yi, LIN Zhi-xiong, GUO Xiao-feng. Pathogenicity and protection in mice of rearranging the M gene of RABV HEP-Flury. Chinese Journal of Zoonoses, 2020, 36(3): 173-177.
[1] Aguemon CT, Tarantola A, Zoumenou E, et al. Rabies transmission risks during peripartum-Two cases and a review of the literature[J]. Vaccine, 2016,34(15):1752-1757. DOI: 10.1016/j.vaccine.2016.02.065 [2] Albertini AA, Ruigrok RW, Blondel D. Rabies virus transcription and replication[J]. Adv Virus Res, 2011,79:1-22. DOI:10.1016/B978-0-12-387040-7.00001-9 [3] Ball LA, Pringle CR, Flanagan B, et al. Phenotypic consequences of rearranging the P, M, and G genes of vesicular stomatitis virus[J]. J Virol, 1999,73(6):4705-4712. [4] Wertz GW, Perepelitsa VP, Ball LA. Gene rearrangement attenuates expression and lethality of a nonsegmented negative strand RNA virus[J]. Proc Natl Acad Sci U S A, 1998,95(7):3501-3506. DOI: 10.1073/pnas.95.7.3501 [5] Flanagan EB, Ball LA, Wertz G W. Moving the glycoprotein gene of vesicular stomatitis virus to promoter-proximal positions accelerates and enhances the protective immune response[J]. J Virol, 2000,74(17):7895-7902. DOI: 10.1128/jvi.74.17.7895-7902.2000 [6] Morimoto K, Kawai A, Sato Y, et al. A unique transcription mode of rabies virus high egg passage-Flury strain detected in infected baby hamster kidney-21 cells[J]. Microbiol Immunol, 2011,55(8):558-564. DOI: 10.1111/j.1348-0421.2011.00354.x [7] Mei M, Long T, Zhang Q, et al. Phenotypic Consequences In vivo and In vitro of Rearranging the P Gene of RABV HEP-Flury[J]. Front Microbiol, 2017,8:120. DOI: 10.3389/fmicb.2017.00120 [8] Mei M, Long T, Zhang Q, et al. Phenotypic Consequence of Rearranging the N Gene of RABV HEP-Flury[J]. Viruses, 2019,11(5):402. DOI:10.3390/v11050402 [9] Yang XF, Peng JJ, Liang HR, et al. Gene order rearrangement of the M gene in the rabies virus leads to slower replication[J]. Virus Dis, 2014,25(3):365-371. DOI: 10.1007/s13337-014-0220-1 [10] Takayama-Ito M, Inoue K, Shoji Y, et al. A highly attenuated rabies virus HEP-Flury strain reverts to virulent by single amino acid substitution to arginine at position 333 in glycoprotein[J]. Virus Res, 2006,119(2):208-215. DOI: 10.1016/j.virusres.2006.01.014 [11] Finke S, Mueller-Waldeck R, Conzelmann KK. Rabies virus matrix protein regulates the balance of virus transcription and replication[J]. J Gen Virol, 2003,84(Pt 6):1613-1621. DOI: 10.1099/vir.0.19128-0 [12] Davis BM, Rall GF, Schnell MJ. Everything you always wanted to know about rabies virus (but were afraid to ask)[J]. Annu Rev Virol, 2015,2(1):451-471. DOI: 10.1146/annurev-virology-100114-055157 [13] Ben KY, Luco S, Besson B, et al. The matrix protein of rabies virus binds to RelAp43 to modulate NF-kappaB-dependent gene expression related to innate immunity[J]. Sci Rep, 2016,6:39420. DOI: 10.1038/srep39420 [14] Besson B, Sonthonnax F, Duchateau M, et al. Regulation of NF-kappaB by the p105-ABIN2-TPL2 complex and RelAp43 during rabies virus infection[J]. PLoS Pathog, 2017,13(10):e1006697. DOI: 10.1371/journal. ppat.1006697 [15] Luco S, Delmas O, Vidalain PO, et al. RelAp43, a member of the NF-kappaB family involved in innate immune response against Lyssavirus infection[J]. PLoS Pathog, 2012,8(12):e1003060. DOI: 10.1371/journal.ppat.1003060 [16] Lay S, Prehaud C, Dietzschold B, et al. Glycoprotein of nonpathogenic rabies viruses is a major inducer of apoptosis in human jurkat T cells[J]. Ann N Y Acad Sci, 2003,1010:577-581. DOI:10.1196/annals.1299.108 [17] Yang Y, Liu W, Yan G, et al. iTRAQ protein profile analysis of neuroblastoma (NA) cells infected with the rabies viruses rHep-Flury and Hep-dG[J]. Front Microbiol, 2015,6:691. DOI: 10.3389/fmicb.2015.00691 [18] Sarmento L, Li X, Howerth E, et al. Glycoprotein-mediated induction of apoptosis limits the spread of attenuated rabies viruses in the central nervous system of mice[J]. J Neurovirol, 2005,11(6):571-581. DOI:10.1080/13550280500385310 [19] Foley HD, McGettigan JP, Siler CA, et al. A recombinant rabies virus expressing vesicular stomatitis virus glycoprotein fails to protect against rabies virus infection[J]. Proc Natl Acad Sci U S A, 2000,97(26):14680-14685. DOI: 10.1073/pnas.011510698 [20] Fu ZF, Dietzschold B, Schumacher CL, et al. Rabies virus nucleoprotein expressed in and purified from insect cells is efficacious as a vaccine[J]. Proc Natl Acad Sci U S A, 1991,88(5):2001-2005. DOI: 10.1073/pnas.88.5.2001