Locating The Dengue Virus’ ‘Achilles Heel’

Scientists in Australia and China have identified an antibody protects against all four types of dengue viruses.

AsianScientist (Dec. 28, 2017) – In a study published in Structure, a team of researchers has identified an antibody that binds to and kills all four types of dengue viruses.

The dengue virus is transmitted by the Aedis aegypti mosquito and causes flu-like symptoms, including muscle aches and fever. There are four strains of dengue viruses, known as serotypes, and collectively they account for approximately 50 to 100 million new infections per year worldwide. In severe cases of dengue hemorrhagic fever, death can occur. Hence, there is an urgent need for medications that protect against dengue virus infection.

In the present study, a team of researchers led by Dr. Daniel Watterson at the University of Queensland (UQ), Australia, and Dr. Li Jie at ZhuJiang Hospital, China, developed an antibody that blocks the entry of all four types of dengue virus into the host cell, an essential step in the virus’ lifecycle.

“As the antibody recognizes all four dengue virus types, it provides the basis of a safe and broad-spectrum anti-dengue therapy, also informing the next generation of dengue vaccines,” said Watterson.

The study further revealed the structural basis of the antibody binding to each of the four dengue viruses, and sheds light on the specific mechanism by which the dengue virus enters cells. This could help explain why some vaccines may not work, while providing a basis for dengue drug design.

Head of UQ’s School of Chemistry and Molecular Biosciences, Professor Paul Young, who is a co-author of the study, said the work identified an important antibody-binding site on the dengue virus.

“We know from other studies that the dengue virus particle expands its outer shell in response to temperature as a sort of breathing,” he said. “But when we looked at the different stages of breathing that have already been recognized, we found that this antibody-binding site was still hidden, so our work indicates that there must be other, more open states of the virus. We have thus identified a new virus control target, a potential Achilles heel.”

Young added that the spread of four distinct dengue virus types had posed significant hurdles to developing effective vaccines, as any potential vaccine candidate must elicit a strong and protective immune response against all four dengue serotypes.

However, some antibody responses had been shown to strengthen the disease. This challenge has hindered dengue vaccine development for more than 60 years.

“Our antibody was shown to inhibit but not enhance dengue virus infection, and so presents exciting opportunities for control,” said Young.

The article can be found at: Li et al. (2017) Structural and Functional Characterization of a Cross-Reactive Dengue Virus Neutralizing Antibody that Recognizes a Cryptic Epitope.


Source: University of Queensland; Photo: Shutterstock.
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