Amino acids at positions 273 and 394 in rabies virus nucleoprotein are important for both evasion of host RIG-I-mediated antiviral response and pathogenicity.
We previously reported that nucleoprotein (N) is related to the different pathogenicities of the virulent rabies virus strain Nishigahara (Ni) and avirulent strain Ni-CE and also that Ni N, but not Ni-CE N, functions to evade retinoic acid-inducible gene I (RIG-I)-mediated innate immunity. There are three amino acid differences between Ni and Ni-CE N (at positions 273, 394 and 395), indicating that one of these mutations or a combination of mutations is important for the pathogenicity and evasion of innate immunity. We generated Ni-CE mutants in which the amino acids in Ni-CE N were replaced with those of Ni in all combinations. Among the mutants, CE(NiN273/394) with mutations at positions 273 and 394 evaded activation of RIG-I-mediated signaling most efficiently and also showed the highest pathogenicity. This correlation reinforces the relation between evasion of host RIG-I-mediated innate immunity and pathogenicity of rabies virus.
Masatani
Tatsunori
T
The United Graduate School of Veterinary Sciences, Gifu University, 1-1 Yanagido, Gifu 501-1193, Japan.
Ito
Naoto
N
Shimizu
Kenta
K
Ito
Yuki
Y
Nakagawa
Keisuke
K
Abe
Masako
M
Yamaoka
Satoko
S
Sugiyama
Makoto
M
D019943:Amino Acid Substitution / Q000235:genetics; D000596:Amino Acids / Q000235:genetics; D000818:Animals; D002460:Cell Line; D006224:Cricetinae; D000071457:DEAD Box Protein 58; D053487:DEAD-box RNA Helicases / Q000276:immunology*; D004195:Disease Models, Animal; D005260:Female; D006801:Humans; D057131:Immune Evasion; D007928:Lethal Dose 50; D051379:Mice; D016297:Mutagenesis, Site-Directed; D019590:Nucleocapsid Proteins / Q000235:genetics / Q000502:physiology*; D011818:Rabies / Q000473:pathology / Q000821:virology; D011820:Rabies virus / Q000235:genetics / Q000472:pathogenicity*; D016019:Survival Analysis; D014774:Virulence; D037521:Virulence Factors / Q000235:genetics / Q000502:physiology*
D000596:Amino Acids; D019590:Nucleocapsid Proteins; D037521:Virulence Factors; C099601:nucleocapsid protein, Rabies virus; C503356:Ddx58 protein, mouse; D000071457:DEAD Box Protein 58; D053487:DEAD-box RNA Helicases