Abstract
SummaryAedes aegypti mosquitoes are responsible for transmitting many medically important viruses such as those that cause Zika and dengue. The inoculation of viruses into mosquito bite sites is an important and common stage of all mosquito-borne virus infections. We show, using Semliki Forest virus and Bunyamwera virus, that these viruses use this inflammatory niche to aid their replication and dissemination in vivo. Mosquito bites were characterized by an edema that retained virus at the inoculation site and an inflammatory influx of neutrophils that coordinated a localized innate immune program that inadvertently facilitated virus infection by encouraging the entry and infection of virus-permissive myeloid cells. Neutrophil depletion and therapeutic blockade of inflammasome activity suppressed inflammation and abrogated the ability of the bite to promote infection. This study identifies facets of mosquito bite inflammation that are important determinants of the subsequent systemic course and clinical outcome of virus infection.
Highlights
The burden of mosquito-borne viral disease is profound
Inhibition of key components of the inflammatory response to the bite reduced leukocyte influx, suppressed viral replication, and increased host survival. These findings identify an important aspect of the host immune response to mosquito bites that inadvertently promotes concurrent arbovirus infection
Mosquito Bites Enhance the Severity of Virus Infection We developed an in vivo model system that makes use Semliki Forest virus (SFV), a mosquito-borne alphavirus that is a close relative of the chikungunya virus (Powers et al, 2001)
Summary
The burden of mosquito-borne viral disease is profound. In recent years there has been a rapid increase in both the incidence and geographical range of such diseases, with spread to more temperate climates becoming more likely. Important viruses spread by arthropods (known as arboviruses) infect hundreds of millions of people each year (Bhatt et al, 2013; Weaver and Lecuit, 2015). This includes the chikungunya and Zika viruses that have recently triggered large-scale epidemics in the Americas (Burt et al, 2012; Gatherer and Kohl, 2016). Arboviruses are an exceptionally large and diverse group of viruses (Elliott, 2014; Gould and Solomon, 2008; Powers et al, 2001) This heterogeneity, combined with the inability to accurately predict future arbovirus epidemics, makes developing and stockpiling specific drugs and vaccines very challenging
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