Comparative pathogenesis of three Mayaro virus genotypes in the cynomolgus macaque
Melissa M Hamilton1, Emily M Webb2, Max C Peterson1
1BIOQUAL Inc., Rockville, MD, 20852, USA.
Abstract:
Mayaro virus (MAYV), a mosquito-borne alphavirus, is considered an emerging threat to public health with epidemic potential. Phylogenetic studies show the existence of three MAYV genotypes. In this study, we provide a preliminary analysis of the pathogenesis of all three MAYV genotypes in cynomolgus macaques (Macaca facicularis, Mauritian origin). Significant MAYV-specific RNAemia and viremia were detected during acute infection in animals challenged intravenously with the three MAYV genotypes, and strong neutralizing antibody responses were observed. MAYV RNA was detected at high levels in lymphoid tissues, joint muscle and synovia over 1 month after infection, suggesting that this model could serve as a promising tool in studying MAYV-induced chronic arthralgia, which can persist for years. Significant leucopenia was observed across all MAYV genotypes, peaking with RNAemia. Notable differences in the severity of acute RNAemia and composition of cytokine responses were observed among the three MAYV genotypes. Our model showed no outward signs of clinical disease, but several major endpoints for future MAYV pathology and intervention studies are described. Disruptions to normal blood cell counts and cytokine responses were markedly distinct from those observed in macaque models of CHIKV infection, underlining the importance of developing non-human primate models specific to MAYV infection.
Insights
Mayaro virus (MAYV) infection in macaques reveals distinct pathogenesis across three genotypes. This study establishes a primate model for MAYV, crucial for understanding chronic arthralgia and developing interventions.
Area of Science:
- Virology
- Immunology
- Primate Models
Background:
- Mayaro virus (MAYV), a mosquito-borne alphavirus, poses an emerging public health threat.
- Phylogenetic analysis identifies three distinct MAYV genotypes.
- Understanding MAYV pathogenesis is critical for public health preparedness.
Purpose of the Study:
- To conduct a preliminary analysis of the pathogenesis of all three MAYV genotypes.
- To evaluate cynomolgus macaques as a model for MAYV infection.
- To investigate MAYV-induced chronic arthralgia.
Main Methods:
- Intravenous challenge of cynomolgus macaques with three MAYV genotypes.
- Monitoring of RNAemia, viremia, and neutralizing antibody responses.
- Analysis of viral RNA distribution in tissues and cytokine profiles.
Main Results:
- Significant RNAemia, viremia, and neutralizing antibody responses were observed across all genotypes.
- MAYV RNA persisted in lymphoid tissues, muscle, and synovia for over a month.
- Leukopenia and distinct cytokine responses were noted, differing from CHIKV models.
Conclusions:
- Cynomolgus macaques provide a suitable model for studying MAYV pathogenesis, including chronic arthralgia.
- Distinct genotype-specific responses highlight the need for MAYV-specific research.
- This model is valuable for future MAYV pathology and intervention studies.
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