Dynamic of Mayaro virus transmission between Aedes aegypti and Culex quinquefasciatus mosquitoes and a mice model

Mayaro virus (MAYV) is transmitted by Haemagogus spp. mosquitoes and has been circulating in Amazon areas in the North and Central West regions of Brazil since the 1980s, with an increase in human case notifications in the last 10 years. MAYV introduction in urban areas is a public health concern once the infection can cause severe symptoms similar to other Alphaviruses. Regarding to urban transmission, studies with Aedes aegypti demonstrate the potential vector competence of the species and the detection of MAYV in urban populations of mosquitoes. Considering the two most abundant urban mosquito species in Brazil, we investigated the dynamics of MAYV transmission by Ae. aegypti and Culex quinquefasciatus in a mice model. Mosquito colonies were artificially fed with blood containing MAYV and infection (IR) and dissemination rates (DR) were evaluated. On the 7th post-infection day (dpi), IFNAR BL/6 mice were made available as a blood source to both mosquitos species. After the appearance of clinical signs of infection, a second blood feeding was performed with a new group of non-infected mosquitoes. RT-q PCR and plaque assay were carried out with animal and mosquitos tissues. We found for Ae. aegypti a IR of 97,5-100% and a DR of 100% in both 7th and 14th dpi. Regarding Cx. quinquefasciatus, the IR found was 13.1-14.81% and DR ranged from 60% to 80%. To evaluate the mosquito-mice transmission rate, 18 mice were evaluated (Test=12 and Control=6) for Ae. aegypti and 12 animals (Test=8 and Control=4) for Cx. quinquefasciatus. All mice bitten by infected Ae. aegypti showed clinical signs of infection while all mice exposed to infected Cx. quinquefasciatus mosquitoes remained healthy. Viremia found in those animals ranged from 2.5 x 108 to 5 x 109 PFU/ml. Ae. aegypti from the second blood feeding showed a 50% infection rate. Our study showed the applicability of an efficient model to complete arbovirus transmission cycle studies and suggests that the Ae. aegypti population evaluated is a competent vector for MAYV highlighting the risk of establishment of MAYV urban cycle. The mice model employed here can be used more extensively for arthropod-vector transmission studies, with laboratory and field mosquito populations, as well as with other arboviruses. Author summaryMayaro virus (MAYV) is an arbovirus maintained mostly in a sylvan cycle in South America, circulating between Haemagogus mosquitoes and wild animals. In Brazil, MAYV has been circulating in the northern region since early 80s, but a substantial increase in human cases has been reported in the past decade. MAYV infections may go undetected, as clinical symptoms are mistaken with other arboviruses already circulating in Brazil, such as dengue (DENV), Zika (ZIKV) and chikungunya (CHIKV) viruses. The introduction of MAYV in other parts of Brazil may result in a public health concern, since the virus will find all favorable conditions in urban settings: high mosquito densities, poor sanitation and uncontrolled urbanization. Therefore, we conducted a study to test the vector competence of MAYV in the two most abundant mosquito species in Brazil: Aedes aegypti and Culex quinquefasciatus. We used an animal model to analyze the dynamics between artificially-infected mosquitos and mice. We fed mosquito colonies with blood containing MAYV and on the 7th day post-infection (dpi), mice were made available as a blood source to both mosquitos species. When these mice display signs of infection, a second blood feeding was performed with a new group of non-infected mosquitoes. We found that Ae. aegypti mosquitoes are very competent in transmitting MAYV, while Cx. quinquefasciatus presented lower rates of infection and dissemination of the virus. All mice bitten by infected Ae. aegypti showed clinical signs of infection. On the other hand, all mice exposed to infected Cx. quinquefasciatus mosquitoes remained healthy. We also found a higher viremia in animals bitten by infected-Ae. aegypti. Overall, our study showed the applicability of an efficient model to complete arbovirus transmission cycle studies and suggests that the Ae. aegypti population evaluated is a competent vector for MAYV highlighting the risk of establishment of MAYV urban cycle.