Amino Acid Mutation in Position 349 of Glycoprotein Affect the Pathogenicity of Rabies Virus

Rabies, caused by rabies virus (RABV), is a zoonotic disease infecting mammals including humans. Studies have confirmed that glycoprotein (G) is most related to RABV pathogenicity. In the present study, to discover more amino acid sites related to viral pathogenicity, artificial mutants have been constructed in G of virulent strain GD-SH-01 backbone. Results showed that pathogenicity of GD-SH-01 significantly decreased when Gly(349) was replaced by Glu(349) through in vivo assays. Gly(349)→Glu(349) of G did not significantly influence viral growth and spread in NA cells. Gly(349)→Glu(349) of G increased the immunogenicity of GD-SH-01 in periphery and induced more expression of interferon alpha (IFN-α) in the brain in mice. It was observed that Gly(349)→Glu(349) of G led to enhanced blood–brain barrier (BBB) permeability at day 5 postinfection. All together, these data revealed that Gly(349)→Glu(349) of G mutation decreased RABV pathogenicity through enhanced immune response and increased BBB permeability. This study provides a new referenced site G349 that could attenuate pathogenicity of RABV.