Transmission Dynamics and Pathogenesis of Contemporary Mayaro Virus Strains.

Project Summary/Abstract. Arboviruses, such as Mayaro virus (MAYV), are emerging with severe impacts on human health. Initially identified in Trinidad and Tobago in 1954, MAYV is widespread in South America, causing outbreaks of febrile illness and chronic, debilitating joint pain. Due to similar symptoms with chikungunya, dengue, and other diseases, along with inadequate surveillance, MAYV infections are underreported despite seroprevalence rates exceeding 50% in some regions. MAYV is typically maintained in a sylvatic transmission cycle involving Haemogogus mosquitoes and various animals, but human-biting mosquitoes like Aedes aegypti, Ae. albopictus, Anopheles albimanus, and An. quadrimaculatus are competent vectors in the laboratory. The recent detection of MAYV in Haiti, an area lacking forests, suggests a shift to urban transmission involving human-biting mosquitoes. However, most studies on MAYV have used historical virus strains, not accounting for potential adaptations in contemporary strains. Our understanding of MAYV's risk of expansion is therefore limited. We propose a proactive approach to evaluate the risk of contemporary MAYV strains. Recent findings of three distinct MAYV lineages in Haiti indicate possible evolutionary adaptations. Given the travel frequency between Hispaniola (the island encompassing Haiti and The Dominican Republic) and North America, the risk of further spread is significant. Here, we propose two aims: In Aim 1, we will develop novel molecular tools for studying MAYV and assess the transmission potential of contemporary, Haitian MAYV strains by widespread mosquito vectors, including field-caught mosquitoes. In Aim 2, we will evaluate the replication and virulence of contemporary MAYV strains in human cells and mice and assess MAYV transmission in a complete transmission cycle between mice and mosquitoes, determining the minimum infectious dose required to infect mosquitoes. This work is vital for understanding MAYV's expansion potential. This study will identify differences between strains that can be used in future studies to identify viral genetic determinants driving changes in transmission or virulence. Finally, the insights gained will contribute significantly to global health, offering novel strategies and tools for arbovirus research.