Mayaro virus pathogenesis and immunity in rhesus macaques

Area of Science:

• Virology
• Immunology
• Pathogenesis

Background:

• Mayaro virus (MAYV) is a mosquito-borne alphavirus causing persistent arthritogenic disease.
• Understanding MAYV pathogenesis in non-human primates (NHP) is crucial for developing effective interventions.

Purpose of the Study:

• To characterize MAYV infection and immune responses in a rhesus macaque model.
• To establish a relevant NHP model for evaluating MAYV therapies and vaccines.

Main Methods:

• Evaluated five MAYV strains in mice to select a virulent strain (BeAr505411).
• Inoculated three rhesus macaques with MAYV strain BeAr505411.
• Assessed viral dissemination, tissue pathology, and immune activation via necropsy and longitudinal blood sampling.

Main Results:

• Peak viremia occurred at 2 days post-infection (dpi), with viral RNA detected in muscles, joints, and various organs up to 10 dpi.
• Histopathology revealed joint and muscle inflammation, with skin lesions and lymphocytic aggregation in affected skin.
• Robust innate and adaptive immune activation, including neutralizing antibodies and elevated inflammatory cytokines, was observed.

Conclusions:

• The rhesus macaque model effectively recapitulates key aspects of human MAYV infection.
• This model provides a valuable platform for preclinical testing of novel MAYV vaccines and therapeutics.
• Findings highlight the potential for MAYV to cause widespread tissue dissemination and significant immune responses.