Evolution of Mayaro virus and its impact on transmission by urban vectors

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Abstract Mayaro virus (MAYV) is the second leading cause of alphavirus-induced febrile illness in South American countries. In recent years, MAYV has gained significant attention because its geographic distribution is expanding north from South and Central America into the Caribbean Islands. While sporadic cases of MAYV were reported in past years, it is still unclear why MAYV outbreaks of considerable proportion are now being recognized more frequently in Latin America and what factors are accounting for the expansion of the virus to new geographic areas. Recently, eco-epidemiological investigations have confirmed the presence of naturally infected Aedes aegypti in Brazil. This raises the possibility that adaptation of MAYV to be better transmitted by urban vectors is a major contributing factor to the emergence and expansion of this pathogen. Thus, studies are urgently needed to assess this possibility. Given the expansion of MAYV into new geographic areas and the evidence supporting urban transmission, we conducted vector competence studies with Aedes aegypti and Aedes albopictus and MAYV strains isolated during years of low (2002) or high MAYV transmission (2011) in Peru. We observed that a MAYV strain isolated during an outbreak in 2011 had greater frequency of infection, dissemination, and transmission in both Aedes aegypti and Aedes albopictus, whereas minimal to no transmission was detected with the strain isolated in 2002, a year of low MAYV transmission. In the studies of this proposal, we hypothesize that MAYV is adapting to be better transmitted by Aedes aegypti and Aedes albopictus and that evolutionary changes in the E2 glycoprotein of the MAYV genome promote enhanced infectivity in these mosquito vectors. We will: 1) examine the vector competence of urban vectors for circulating MAYV strains in Peru, using a susceptible animal model and 2) conduct genetic studies to assess E2 glycoprotein mutations and their contribution to vector competence. Completion of this study will provide critical knowledge to our understanding of MAYV transmission and will identify and experimentally validate viral genes associated with enhanced transmission. It will also generate powerful tools, including the development of reverse genetic systems, for studying other aspects of MAYV infection. Therefore, this project represents an important step towards our long-term objective of understanding the emergence mechanism of MAYV.