The inoculation of viruses into mosquito bite sites is an important and common stage of arbovirus infections. This schematic depicts the findings of McKimmie and colleagues, who show that inflammation at bite sites aids viral replication and dissemination in vivo, resulting in more severe infection. These findings define additional targets for postexposure prophylactic intervention. [Pingen et al./Immunity 2016]
The raised red welts and searing itch that result from the bite of insidious mosquitos may, according to recently published data, help any viruses the insect is carrying pass on to a new host. A team of researchers led by investigators at the University of Leeds suggests that the swelling and irritation that make mosquito bites so unpleasant may provide a mechanism by which viruses like Zika, dengue, and chikungunya are able to replicate and spread.
“Mosquito bites are not just annoying—they are key for how these viruses spread around your body and cause disease,” explained senior study author Clive McKimmie, Ph.D., research fellow at the University of Leeds. “We now want to look at whether medications such as anti-inflammatory creams can stop the virus establishing an infection if used quickly enough after the bite inflammation appears.”
Dr. McKimmie added that “before we did this study, little was known about the events and processes that occur at mosquito bite sites. Our findings suggest that the inflammatory response at these sites helps viruses to replicate, enhancing their ability to cause disease.”
The results of this study were published recently in the journal Immunity in an article entitled “Host Inflammatory Response to Mosquito Bites Enhances the Severity of Arbovirus Infection.”
In the new research, the investigators used mouse models to study the bites of the Aedes aegypti mosquito—the species responsible for carrying many virulent viral strains. When a mosquito like Aedes bites, it injects saliva into the skin, triggering an immune response that causes neutrophils and myeloid cells rush to the site.
In the current study, the team injected mice with viruses into the skin with or without the presence of a mosquito bite at the injection site and compared the reaction. Interestingly, they found that instead of helping, some of these immune cells get infected and inadvertently replicate virus.
Conversely, in the absence of mosquito bites and their accompanying inflammation, the viruses failed to replicate well. But the presence of mosquito bites at the infection site resulted in an order-of-magnitude higher levels of virus. Further studies showed that the influx of white blood cells was required for enhanced replication of the viruses.
“We think the bite itself is affecting the systemic course and clinical outcome of the infection,” Dr. McKimmie noted. “If you want an in vivo model that replicates the most relevant parts of infection, you should include this inflammatory aspect.”
Dr. McKimmie added that “this was a big surprise we didn't expect. These viruses are not known for infecting immune cells. And sure enough, when we stopped these immune cells from coming in, the bite did not enhance the infection anymore.”
While the research is still preliminary and the researchers caution over interpretation of the results, they did note that their findings may suggest new approaches for combating viruses.
“This research could be the first step in repurposing commonly available anti-inflammatory drugs to treat bite inflammation before any symptoms set in,” Dr. McKimmie remarked. “We're quite keen to see if using topical creams to suppress bite inflammation will enable you to stop a virus from making someone as sick as it otherwise would do.”
If proven effective, this approach could work against future virus outbreaks that we have yet to encounter and would pose as potential threats to public health.