UNDERSTANDING THE EFFECTS OF ENVIRONMENTAL VARIATION ON VECTOR-VIRUS INTERACTIONS AND TRANSMISSION IN THE ZIKA VIRUS SYSTEM

Zika virus (ZIKV) is an arbovirus primarily transmitted by Aedes mosquitoes. ZIKV typically causes asymptomatic infections or relatively mild symptoms. However, ZIKV infection during pregnancy can lead to congenital Zika syndrome, a unique pattern of birth defects and disabilities. In 2016, introduction of ZIKV into naïve and susceptible populations quickly reached epidemic levels and spread to more than 65 countries worldwide. As this was the first time that severe disease outcomes were linked to ZIKV infection, therapeutics, vaccines, and even solid diagnostic tools were not available. There was an immediate need for their development, but also an urgent need to control and limit ZIKV transmission, to understand the main drivers for viral spread, and to predict potential spreading patterns. There are multiple factors that affect the transmission dynamics of arboviruses such as Zika. Epidemiological outcome of disease depends on the pathogen-host interactions that are defined by numerous intrinsic factors such as pathogen and host genetics, as well as extrinsic biotic and abiotic factors. Environmental factors can have direct effect on virus replication and infection outcome or indirect effect due to altered physical barrier, immune response, and overall host fitness. There are also various socioeconomic factors and human behaviors that can shape transmission. We demonstrated that increasing ZIKV dose in the blood-meal significantly increases the probability of mosquitoes becoming infected and infectious. Using these data to parameterize an R0 model, we showed that increasing viremia from 104 to 106 PFU/mL increased relative R0 3.8-fold, demonstrating that variation in viremia substantially affects transmission risk. Temperature is known to be one of the strongest drivers of vector-borne transmission. We used a temperature-dependent model to infer temperature effects on ZIKV transmission and showed that transmission was optimized at 29C, and had a thermal range of 22.7C - 34.7C. We have also demonstrated why ZIKV transmission is ineffective at cool temperatures and how temperature alters ZIKV replication in mosquito cells. Assessing how biotic and abiotic factors alter our standard formulation of vectorial capacity and model predictions is critical in order to predict the seasonality and geography of ZIKV spread so we can deploy effective disease interventions.