For a lot of people, getting bitten by a mosquito is an unpleasant experience, leaving an angry red wheal that can last a few days. But aside from the irritation and itchiness it can cause, could the inflammation from bites actually make infections spread by mosquitoes worse? Today at the Society’s International Meeting on Arboviruses and their Vectors, Dr Clive McKimmie will talk about his group’s research on immune responses to mosquito bites and how the bites themselves may be involved in viral disease.
The mouthparts of blood-sucking mosquitoes are specially adapted to pierce the skin of their hosts, root around for a vessel, and feed off the blood inside. But a mosquito bite is not one-way traffic – in addition to sucking up blood, the insect also pumps saliva into the bite, which contains a cocktail of proteins designed to override the host’s defences. These include anti-coagulants to prevent blood clotting and agents to stop the blood vessels narrowing, allowing the mosquito to feed for as long as possible. It’s our immune reaction to these saliva proteins that ultimately causes the redness and inflammation that can occur after being bitten.
If a mosquito is infected with a virus, this microbial hitchhiker can use the insect’s bite as a transport method, allowing it to move into the host. These viruses are known as arthropod-borne viruses, or arboviruses for short. This group of viruses contains many important human pathogens, including those that cause dengue fever, yellow fever and chikungunya, which are all spread by Aedes mosquitoes. Recent estimates suggest there may be up to 400 million such infections per year.
Clive’s team has been investigating the body’s immunological responses to mosquito bites and how they may shape the course of an arboviral infection. According to their initial findings, the presence of a bite enhances the spread of infection in mice. The team introduced Semliki Forest Virus (SFV), an arbovirus related to chikungunya, into mice, either at the site of a mosquito bite or by inoculating the virus into an unbitten mouse. They were then able to track where and how quickly the virus spread, using a genetically modified virus that emits light inside infected cells.
“We have very sensitive cameras which can detect the virus as it replicates inside a live mouse,” Clive says. “It’s a bit like seeing the glow of a torch through your fingers.”
They found that when the virus was transmitted with a mosquito bite, viral replication was increased, symptoms were more severe and mice were more likely to die from infection. In the case of SFV, the virus spreads to the brain and causes an inflammation in the tissues, known as encephalitis.
The reason for this seems to be the immune response of mice to the bite. The team determined which immune cells and molecules were important in causing the post-bite inflammation and found that when they therapeutically inhibited these responses, the bites no longer enhanced infection.
“We think the inflammation from the bite attracts certain white blood cells called myeloid cells, which the virus particularly likes to infect. So the bite helps the virus by bringing in cells which it can infect and replicate in.” Clive explains.
Historically, arboviruses have largely been studied by simply injecting them into hosts, so the contribution of the mosquito bite has been missed – even though it is how the virus is transmitted in the wild. The team hopes that their research could open up new ways to treat the many different kinds of arbovirus infections, because the bite is common to all of them. For example, a cream that targets specific processes within the bite could dampen the spread of infection, meaning it could be used to treat multiple arboviruses in the same way. Alternatively, it could turn out that the severity of someone’s reaction to a bite is a good indicator of their likely outcome to infection – which would be invaluable information for clinicians.
“We don’t properly understand what happens in the skin when a mosquito bites you and transmits a virus, which is extraordinary when you consider the number of infections worldwide,” Clive says. “But by bringing expertise on inflammation and virus infection together, we can look at things in a different way. We’re really excited about what this work could mean for future research and new treatments.”
To find out more about the work of Clive’s team, visit www.virus-host-interactions.org