Mosquito saliva study opens new doors for blocking Zika, Dengue, and West Nile infections

Mosquitoes do more than simply transmit the viruses they carry: their saliva may actively help these viruses establish infection in the body from the very moment of the bite. This is the finding of a study conducted by a team from the IRD, CNRS, the University of Montpellier (France), and Mahidol University (Thailand), published in Nature Communications. The scientists identified a viral compound in the saliva of infected mosquitoes that appears to promote infection by inhibiting the body's initial immune response. This discovery opens the door to a new vaccination strategy against mosquito-borne viruses.

A public health issue that remains poorly understood

Dengue, Zika, West Nile fever… Orthoflaviviruses transmitted by mosquitoes represent a major public health threat, particularly in tropical and subtropical regions (Asia, South America, Africa). Dengue, Zika, and West Nile viruses alone are responsible for around 500 million infections every year. All of these viruses share one common feature: they are transmitted through mosquito bites. Yet there is still no effective treatment covering all of these diseases, and the mechanisms that allow the virus to establish itself in the skin after a bite remain largely unclear.

Understanding how mosquito saliva influences skin infection is essential for better understanding transmission and identifying new prevention targets."

Julien Pompon, Research Director at IRD and Flavivaccine Coordinator

A compound in saliva "sets the stage" for infection

When an infected mosquito bites the skin, it injects saliva containing viral particles. The researchers discovered that this saliva also contains a viral RNA (ribonucleic acid), known as sfRNA, which plays an active role in establishing infection. Using an in vivo transmission model developed at Vectopôle, an IRD laboratory based in Montpellier dedicated to vector research, the scientists demonstrated that the greater the amount of sfRNA present in the saliva, the more strongly infection is promoted.

Beyond helping establish infection, sfRNA also enhances viral spread. When a virus enters the skin, the human body triggers an innate immune response aimed at detecting the virus and limiting its replication. However, the researchers showed that once injected through saliva, sfRNA inhibits activation of this immune response, allowing the viruses to gain time at the bite site.

From the laboratory to a new vaccination strategy

The mechanism was studied in two orthoflaviviruses transmitted by two different mosquito species: West Nile virus transmitted by common mosquitoes (Culex), and Zika virus (ZIKV) transmitted by tiger mosquitoes (Aedes). In both cases, researchers detected sfRNA in the saliva of infected mosquitoes. These findings suggest that the presence of this RNA in saliva may be a shared mechanism among several orthoflaviviruses, raising the possibility of common prevention strategies targeting not a specific virus, but rather the mechanism that facilitates infection at the time of the bite.

This discovery shows how fundamental research into transmission mechanisms can lead to a new preventive approach against several mosquito-borne viral diseases."

Julien Pompon, Research Director at IRD and Flavivaccine Coordinator

Building on this discovery, IRD researchers have developed a vaccination strategy targeting the identified salivary compound. This approach is currently being developed and optimized for clinical-scale application as part of the Horizon Europe Flavivaccine project (https://flavivaccine.eu/), which aims to explore a prevention strategy against several endemic diseases affecting countries in the Global South.