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

Michiko Harada1,2, Aya Matsuu1, Yoshihiro Kaku1

  • 1Department of Veterinary Science, National Institute of Infectious Diseases, 1-23-1 Toyama, Tokyo 162-8640, Japan.

Viruses
|May 25, 2024
PubMed

Insights

A single mutation in the rabies virus (RABV) matrix protein, M(D80N), enhances viral neurovirulence in mice. This adaptation to mouse neuronal cells increases viral replication and causes significant weight loss.

Area of Science:

  • Virology
  • Neuroscience
  • Infectious Diseases

Background:

  • Rabies virus (RABV) causes fatal encephalitis and is highly neurotropic.
  • The HEP-Flury strain was adapted to mouse neuroblastoma (MNA) cells.
  • Recombinant strains are crucial for studying viral adaptation and virulence.

Purpose of the Study:

  • To compare the growth of a recombinant HEP (rHEP) strain with the original HEP strain.
  • To investigate the role of a specific mutation in the matrix (M) protein in viral neurovirulence.

Main Methods:

  • Comparison of viral titers between original HEP and rHEP strains after MNA cell culture.
  • Genetic sequencing to identify mutations in the M protein.
  • Intracerebral inoculation of mice with rHEP and rHEP-M(D80N) strains.
  • Assessment of viral antigen in mouse brains and monitoring of body weight.

Main Results:

  • The original HEP strain showed a higher titer than rHEP.
  • A single amino acid substitution, M(D80N), was identified in the M protein of the adapted HEP strain.
  • Mice inoculated with rHEP-M(D80N) exhibited increased viral growth in the brain and significant weight loss.
  • Higher viral antigen-positive cells were observed in brains infected with rHEP-M(D80N) compared to rHEP.

Conclusions:

  • A single amino acid substitution (M(D80N)) in the RABV matrix protein is associated with enhanced neurovirulence in mice.
  • This mutation facilitates viral adaptation to mouse neuronal cells, leading to increased pathogenicity.
Keywords:
amino acid substitutionmatrix proteinmouse neuroblastoma cellrabies virus

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