Campus researchers identify important dengue virus molecule

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Campus researchers have identified a key molecule responsible for the pathogenesis of severe cases of dengue virus infections.

Led by molecular virologist and UC Berkeley School of Public Health professor Eva Harris, a team of six researchers published a study this week showing that a protein called NS1,or nonstructural protein 1, instigates the leakage of fluid from blood vessels, which causes most fatalities from dengue infections. Their findings could further enhance dengue-related research and provide avenues for clinical response through the development of NS1-based vaccines and therapeutic drugs.

Transmitted by the Aedes mosquito, dengue is a tropical virus that infects 390 million people annually and currently has no treatment. Approximately one-fourth of dengue infections result in dengue fever, or “breakbone” fever, a flu-like illness with symptoms including rashes and intense joint and muscle pain.

While the symptoms of dengue fever can subside, nearly 500,000 cases of infection develop into a more severe infection known as dengue hemorrhagic fever and dengue shock syndrome, which can become fatal within 48 hours. Dengue shock syndrome-related fatalities are the result of vascular leakage — the leakage of essential bodily fluids from blood vessels that leads to abnormally low blood pressure.

“We don’t immediately know which of the 100 million cases will result in fatalities,” Harris said. “This is distressing from both a medical and population perspective.”

Conducting experiments on mice and on epithelial cells from the blood vessels of human lungs, Harris and her team concluded that the vascular leakage characteristic of dengue hemorrhagic fever is partially caused by the NS1 molecule.

Once the team inoculated mice with the NS1 protein and, eight weeks later, gave mice a lethal dose of the dengue virus, the team observed that the mice developed a resistance to the disease, providing evidence that NS1 could become an effective component of potential dengue vaccines.

The team’s research also suggests that targeting the protein with therapeutic drugs could reduce the vascular leakage that causes most dengue-related fatalities and provide opportunities for clinical development, said UC Berkeley doctoral student and fellow author of the study Dustin Glasner.

But both Glasner and Harris noted that obstacles still remain — namely translating their research into readily available medical products for dengue victims and those seeking vaccines.

Glasner said there is not only a challenge to jump from mice to humans but also to obtain funding, which largely comes from American and European sources, for research on a disease that mostly affects those in comparatively impoverished tropical countries. The World Health Organization has classified dengue as one of 17 neglected tropical diseases.

“The science is the fun stuff,” Harris said. “What will be a major challenge is taking our work from the bench to the bedside.”

Contact Ishaan Srivastava at [email protected] and follow him on Twitter at @ishaansriv.