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FASEB journal : official publication of the Federation of American Societies for Experimental Biology
07, 2020;34 (7): 9650-9663.

Single amino acid change at position 255 in rabies virus glycoprotein decreases viral pathogenicity.

Jun Luo, Boyue Zhang, Ziyu Lyu, Yuting Wu, Yue Zhang, Xiaofeng Guo
Author Information
  1. Jun Luo: College of Veterinary Medicine, South China Agricultural University, Guangzhou, China.
  2. Boyue Zhang: College of Veterinary Medicine, South China Agricultural University, Guangzhou, China.
  3. Ziyu Lyu: College of Veterinary Medicine, South China Agricultural University, Guangzhou, China.
  4. Yuting Wu: College of Veterinary Medicine, South China Agricultural University, Guangzhou, China.
  5. Yue Zhang: College of Veterinary Medicine, South China Agricultural University, Guangzhou, China.
  6. Xiaofeng Guo: College of Veterinary Medicine, South China Agricultural University, Guangzhou, China.
PMID: 32469133 DOI: 10.1096/fj.201902577R

Abstract

Previous studies have indicated that the amino acid at position 333 in the glycoprotein (G) is closely related to rabies virus (RABV) pathogenicity. However, whether there are other amino acid residues in G that relate to pathogenicity remain unclear. The aim of this study is to find new amino acid residues in G that could strongly reduce RABV pathogenicity. The present study found that the pathogenicity of a virulent strain was strongly attenuated when the amino acid glycine (Gly) replaced the aspartic acid (Asp) at position 255 in G (D255G) as intracranial (i.c.) infection with this D255G mutant virus did not cause death in adult mice. The indexes of neurotropism of the D255G mutant strain and the parent GD-SH-01 are 0.72 and 10.0, respectively, which indicate that the D255G mutation decreased the neurotropism of RABV. In addition, the D255G mutation significantly decreased RABV replication in the mouse brain. Furthermore, the D255G mutation enhanced the immune response in mice, which contributed to the clearance of RABV after infection. The Asp255 → Gly255 mutation was genetically stable in vitro and in vivo. In this study, we describe a new referenced amino acid site in G that relates to the pathogenicity of RABV.

Keywords

glycoprotein mutation pathogenicity rabies virus vaccine

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MeSH Term

Amino Acid Substitution
Amino Acids
Animals
Disease Models, Animal
Glycoproteins
Mice
Mutation
Neuroblastoma
Rabies
Rabies virus
Viral Proteins
Virulence

Chemicals

Amino Acids
Glycoproteins
Viral Proteins
Journal Article Research Support, Non-U.S. Gov't

Word Cloud

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