Inflammation from Mosquito Bites May Enhance Virus Replication, Dissemination

According to a mouse study published this week in the journal Immunity , the swelling and irritation that make mosquito bites so unpleasant may provide a mechanism by which any viruses the mosquito is carrying are able to replicate and spread.

Inflammation from Mosquito Bites May Enhance Virus Replication, Dissemination

The inoculation of viruses into mosquito bite sites is an important and common stage of arbovirus infections. Dr. McKimmie and his colleagues show that inflammation at bite sites aids viral replication and dissemination in vivo, resulting in more severe infection. These findings define additional targets for post-exposure prophylactic intervention. Image credit: Marieke Pingen et al.
“Before we did this study, little was known about the events and processes that occur at mosquito bite sites,” said senior author Dr. Clive McKimmie, from the University of Leeds, UK.
“Our findings suggest that the inflammatory response at these sites helps viruses to replicate, enhancing their ability to cause disease.”
In this study, the scientists used mouse models to study the bites of the Aedes aegypti mosquito.
“ Aedes aegypti mosquitoes are responsible for transmitting many medically important viruses such as those that cause Zika and dengue,” they explained.
“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 .”
When a mosquito bites, it injects saliva into the skin. The saliva triggers an immune response, in which white blood cells called neutrophils and myeloid cells rush to the site.
In the study, Dr. McKimmie and co-authors injected mice with Semliki Forest and Bunyamwera viruses into the skin with or without the presence of a mosquito bite at the injection site and compared the reaction.
They found that instead of helping, some of these immune cells get infected and inadvertently replicate virus.
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 said.
“If you want an in vivo model that replicates the most relevant parts of infection, you should include this inflammatory aspect.”
“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.”
Although this research is still early work done in mice, the finding suggests new approaches for combating viruses that lead to health problems in humans.
“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,” Dr. McKimmie said.
“If it’s proven effective, this approach could work against future virus outbreaks that we don’t know about yet.”
“Nobody expected Zika, and before that nobody expected chikungunya,” he added.
“There are estimated to be hundreds of other mosquito-borne viruses out there and it’s hard to predict what’s going to start the next outbreak.”