How Do Virus-Mosquito Interactions Lead to Viral Emergence?

Abstract

Arboviruses such as West Nile, Zika, chikungunya, dengue, and yellow fever viruses have become highly significant global pathogens through unexpected, explosive outbreaks. While the rapid progression and frequency of recent arbovirus outbreaks is associated with long-term changes in human behavior (globalization, urbanization, climate change), there are direct mosquito-virus interactions which drive shifts in host range and alter virus transmission. This review summarizes how virus-mosquito interactions are critical for these viruses to become global pathogens at molecular, physiological, evolutionary, and epidemiological scales. Integrated proactive approaches are required in order to effectively manage the emergence of mosquito-borne arboviruses, which appears likely to continue into the indefinite future.

Keywords: arboviruses; mosquitoes; virus emergence; virus evolution; virus–mosquito interactions.

Figure 1. Different tissue barriers determine vector competence in mosquitoes

An arbovirus is taken up by the mosquito during an infectious bloodmeal. The virus infects the midgut epithelium and replicates before it passes the basal lamina into the hemolymph and disseminates throughout the mosquito body. In order to be transmitted to the next host, the virus has to infect the salivary glands from where it can be released into the saliva and transmitted to the next host. Virus population genetic diversity is reduced stochastically as viruses pass through anatomical barriers to transmission, such as midgut infection and escape barriers, and salivary gland infection and escape barriers. Potential changes in virus populations that have passed through such bottlenecks are depicted as a change in color (increasingly dark blue). Through this genetic drift as well as positive selection in the mosquito, new genotypes may emerge.

Figure 2. Key Figure. Summary of factors influencing arbovirus emergence

Cellular and molecular interactions such as RNAi drive virus diversification in the mosquito. Differences in mosquito vector competence and bottlenecks that the virus encounters during dissemination within a mosquito can result in further divergence of the virus population and drive virus evolution and emergence. Due to urbanization and deforestation humans and livestock are frequently in close proximity to mosquito vectors and vertebrate hosts maintaining viruses in sylvatic/enzootic transmission cycles. Human settlements may also bring along anthropophagic mosquitoes such as Aedes aegypti and Aedes albopictus, which may encounter viremic reservoir hosts, such as primates. Interactions between new vector mosquitoes and vertebrate hosts can drive arbovirus evolution and emergence. Due to intense travel and ubiquitous distribution of Aedes spp. mosquitoes, such spillover events may easily lead to the outbreak of a new global pathogen.

Figure 3. Vectorial capacity

The vectorial capacity formula describes the total number of future infectious bites arising from mosquitoes biting an individual infectious host on a single day. It consists of five factors: vector density with respect to host (m), the daily probability of the host being fed upon (a), vector competence of the mosquito population (VC), the probability of daily survival (p) and the extrinsic incubation period (n). None of these factors are constants, but variables which depend on both environmental influences as well as specific virus-mosquito interactions as indicated.