Single Amino Acid Substitution in the Matrix Protein of Rabies Virus Is Associated with Neurovirulence in Mice

Rabies is a fatal zoonosis caused by the rabies virus (RABV), with 59,000 cases reported annually worldwide. The viral genome of RABV encodes N, P, M, G, and L structural proteins. The authors created a recombinant HEP (rHEP) based on the sequence of the rabies vaccine strain, HEP-Flury, and compared the growth of the two strains in MNA cells. They found a single amino acid substitution in the M protein (D80N) between the two strains and created rHEP-M(D80N). Mice inoculated with rHEP-M (D80N) showed significant weight loss compared to mice inoculated with rHEP. Furthermore, antigen levels in mouse brain were significantly higher in mice inoculated with rHEP-M(D80N). These results indicate that a single amino acid substitution in the M protein is important in the neuropathogenesis of RABV.
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