The structure and function of a pupal cuticle protein in the exoskeleton—a tough covering that supports and shields the bodies of some invertebrate animals, particularly arthropods—of Aedes aegypti mosquitoes have been uncovered by NUS scientists, and this discovery may one day contribute to the prevention of dengue virus infection.
Humans can contract dengue fever from the dengue virus, which belongs to the genus Flavivirus, when they are bitten by an infected female Aedes aegypti mosquito. Over 5 million cases of dengue fever were reported worldwide in 2023. As of right now, there is no known cure for dengue fever, and the only dengue vaccination—Dengvaxia—is reserved for kids who have already contracted the virus and reside in dengue-endemic areas.
In an effort to clarify how cuticle proteins present in Aedes aegypti mosquitoes can prevent and regulate the infection of a mosquito-borne virus called dengue virus, Professor J Sivaraman and his colleagues from the Department of Biological Sciences within the NUS Faculty of Science set out to investigate this.
The results, which were reported in Protein Science, point to this cuticle protein’s potential as a target for the development of novel strategies to manage dengue virus infection.
The female Aedes aegypti mosquito may hold the key to developing novel antiviral treatments to manage dengue virus infection, notwithstanding its function as a dengue virus carrier.
Previous studies have discovered that this same mosquito’s cuticle proteins interact with the surface proteins of mosquito-borne viruses, like the Zika and West Nile viruses, to prevent infection.
There are four types of dengue virus: DENV-1, DENV-2, DENV-3, and DENV-4.
In this NUS study, the researchers investigated how a cuticle protein prevents the DENV-2 type from infecting host cells at the molecular level.
The NUS researchers used a method called Nuclear Magnetic Resonance (NMR) spectroscopy, which analyzes the molecular structure of the cuticle protein using a strong magnetic field, to start investigating the role of the cuticle protein in preventing dengue virus infection. They discovered that the protein adopts a disordered structure.
The NUS team proposed that the cuticle protein inhibits dengue virus infection by means of a dual strategy after doing additional analysis of the molecular interactions between the virus and the protein.
In order to stop a viral infection, the cuticle protein first binds directly to the dengue virus, causing it to clump and preventing the virus from interacting with the host cells. Scientists at NUS have determined the precise sites where the cuticle protein and virus interact throughout their investigation.
Second, the cuticle protein may contribute to the presentation of the dengue virus antigen to immune cells as an anti-viral tactic to inhibit viral detection and attachment. This is achieved by interactions with immune cell surface receptors, which can prevent dengue virus infection.
The results suggest that the protein found in the pupal cuticle may be a target for the development of inhibitors or antibodies to manage dengue virus infection. These discoveries pave the way for innovative anti-viral approaches and advance our knowledge of the molecular dynamics of mosquito-virus interactions, according to Prof. Sivaraman.