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Evolution of Rabies Virus Isolates: Virulence Signatures and Effects of Modulation by Neutralizing Antibodies
Juliana Amorim Conselheiro1, Gisely Toledo Barone1, Sueli Akemi Taniwaki Miyagi2
1Laboratory of Diagnostics of Zoonosis and Vector-borne Diseases (LabZoo), Zoonosis Surveillance Division, Health Surveillance Coordination, Municipal Health Department, São Paulo 02031-020, SP, Brazil.
Pathogens (Basel, Switzerland)
|December 23, 2022
Summary
Rabies virus (RABV) evolves through mutations, forming viral quasispecies. Key glycoprotein mutations at positions 186 and 188 significantly impact RABV virulence and antibody resistance.
Area of Science:
- Virology
- Molecular Biology
- Immunology
Background:
- Rabies virus (RABV), an RNA virus, exhibits a quasispecies structure due to its error-prone RNA polymerase, enabling adaptation.
- Understanding the molecular basis of RABV virulence is crucial for developing effective control strategies.
Purpose of the Study:
- To identify gene signatures associated with RABV virulence modulation.
- To investigate the role of nucleoprotein and glycoprotein genes in RABV evolution under varying selective pressures.
Main Methods:
- Serial passage of RABV lineages in neuronal cell systems.
- In vitro evolution experiments with and without neutralizing antibodies.
- Analysis of replicative fitness, in vivo neurotropism, and protein structure-dynamics.
Main Results:
- Amino acid positions 186 and 188 in the RABV glycoprotein were identified as critical virulence factors.
- Site 186 may facilitate attachment to heparan sulfate as a secondary receptor.
- Polymorphism at position 333 contributes to the selection of escape mutants against neutralizing antibodies.
Conclusions:
- Specific mutations in the RABV glycoprotein directly influence viral virulence.
- These findings provide insights into RABV adaptation mechanisms and potential targets for therapeutic interventions.
