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Phenotypic Consequence of Rearranging the N Gene of RABV HEP-Flury

College of Veterinary Medicine, South China Agricultural University, Guangzhou 510642, China
Guangdong Inspection and Quarantine Technology Center, Guangzhou 510623, China
Authors to whom correspondence should be addressed.
These authors contributed equally to this work.
Present address: Department of Microbiology, Faculty of Medicine, The Chinese University of Hong Kong, Hong Kong Special Administrative Region, China.
Viruses 2019, 11(5), 402;
Received: 4 March 2019 / Revised: 20 April 2019 / Accepted: 25 April 2019 / Published: 29 April 2019
(This article belongs to the Section Animal Viruses)
PDF [3206 KB, uploaded 29 April 2019]


Nucleoprotein (N) is a key element in rabies virus (RABV) replication. To further investigate the effect of N on RABV, we manipulated an infectious cDNA clone of the RABV HEP-Flury to rearrange the N gene from its wild-type position of 1 (N-P-M-G-L) to 2 (P-N-M-G-L), 3 (P-M-N-G-L), or 4 (P-M-G-N-L), using an approach that left the viral nucleotide sequence unaltered. Subsequently, viable viruses were recovered from each of the rearranged cDNA and examined for their gene expression levels, growth kinetics in cell culture, pathogenicity in suckling mice and protection in mice. The results showed that gene rearrangement decreased N mRNA transcription and vRNA replication. As a result, all viruses with rearranged genomes showed worse replication than that of rHEP-Flury in NA cells at a MOI of 0.01, but equivalent or slightly better replication levels at a MOI of 3. Consequently, the lethality in suckling mice infected with N4 was clearly attenuated compared with rHEP-Flury. However, the protection to mice was not enhanced. This study not only gives us insight into the understanding of the phenotype of RABV N gene rearrangement, but also helps with rabies vaccine candidate construction. View Full-Text
Keywords: HEP-Flury; rabies virus; gene rearrangement; nucleoprotein HEP-Flury; rabies virus; gene rearrangement; nucleoprotein

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Mei, M.; Long, T.; Zhang, Q.; Zhao, J.; Tian, Q.; Peng, J.; Luo, J.; Jiang, H.; Lin, Y.; Lin, Z.; Guo, X. Phenotypic Consequence of Rearranging the N Gene of RABV HEP-Flury. Viruses 2019, 11, 402.

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