West Nile virus can be stopped at level of insects by using insulin to boosts their immune response, study shows
Insulin can increase mosquitoes' immunity to West Nile virus which is the leading cause of mosquito-borne disease in the US, a new study has shown.
The findings have the potential to inhibit the spread of West Nile virus (WNV), as well as dengue and Zika viruses, according to researchers from the Washington State University (WSU). Since there are no medications to treat these viruses in people currently, experts say if the infection can be stopped at the level of the mosquito, then humans will not get the virus.
The researchers demonstrated that mammalian insulin increased the insects' ability to suppress the viruses by activating an "antiviral immunity pathway (JAK/STAT)" in mosquitoes. "We show that after mosquitoes take a blood meal containing mammalian insulin, flavivirus replication is reduced in the mosquitoes. This occurs through a newly discovered mechanism whereby insulin signaling activates canonical JAK/STAT signaling," Alan G. Goodman, assistant professor at the School of Molecular Biosciences, WSU, told MEA WorldWide (MEAWW).
According to the researchers, this is a significant step toward the long-term goal of creating an intervention.
"The study will show that new methods exist to reduce flavivirus infections in mosquitoes. Policymakers can now invest in these new methods and combine our new with existing methods of preventing mosquito-borne viral infections," Goodman told MEAWW.
How dangerous are these viruses?
The World Health Organization (WHO) estimates that more than half of the world's population is at risk for contracting a vector-borne disease. Mosquito bites are the most common way humans are infected with flaviviruses, a virus family that includes West Nile, dengue, and Zika. In humans, both West Nile and dengue can result in severe illness and even death. Zika has been linked to birth defects when pregnant women are infected.
According to the US Centers for Disease Control and Prevention (CDC), cases of West Nile virus occur during mosquito season, which starts in the summer and continues through fall. There are no vaccines to prevent or medications to treat in people. About 1 in 5 people, who are infected develop a fever and other symptoms, estimates CDC. Further, about 1 out of 150 infected people develop a serious, sometimes fatal illness.
The study states that since 1999, WNV infection has caused disease in the 48 continental states, frequently resulting in mild febrile symptoms. In more extreme cases, WNV causes neuroinvasive infection with severe complications and long-term patient consequences, including paralysis.
"In 2017, the CDC reported 2,097 cases of human WNV infection in the US, with 68% being classified as neuroinvasive. Dengue virus affects 390 million people worldwide each year. Zika virus, another arbovirus with significant health impacts, was originally confined to small outbreaks but expanded rapidly to more than 30 countries between 2015 and 2016," says the study published in Cell Reports.
Currently, there are no post-exposure therapeutics or effective vaccines against these viruses, indicating an unmet need in public health.
"It's really important that we have some sort of protection against these diseases because currently, we don't have any treatments. If we are able to stop the infection at the level of the mosquito, then humans wouldn't get the virus," says Laura Ahlers, the study's lead author and a recent Ph.D. graduate from WSU. Ahlers is now a post-doctoral fellow with the National Institutes of Health in Bethesda, Maryland.
The study
The research team first worked with fruit flies, which have similar immune responses to mosquitoes. They identified an insulin-like receptor in the insects that, when activated, inhibits the replication of the West Nile virus in the flies. The researchers then elicited the same response in mosquitoes by feeding them blood containing elevated insulin.
Subsequent tests, says the team, showed that "activating this receptor was also effective in suppressing dengue and Zika in insect cells."
The scientists say this is the first time that insulin's connection to a particular immune response pathway, called JAK/STAT, has been identified.
"Our data suggest insulin activates known immune response pathways in vitro and in vivo for overall host restriction of flavivirus infection," the findings state.
According to the research team, if the mosquitoes are carrying less virus when they bite, they will transmit less of the virus, and there will be a better chance that a person will not get the disease.
"We plan to further dissect the mechanisms of insulin signaling and use small molecules to target the proteins in the pathway to inhibit flaviviral infections in mosquitoes and mammals," Goodman told MEAWW.