High levels of hyaluronan polysaccharide in serum from patients infected with dengue virus predict severe disease and contribute to increased blood vessel leakage


Dengue virus infection is transmitted by mosquitoes and is increasing rapidly in the world due to global warming and travel abroad. The infection causes suffering, consumes medical care resources, and can sometimes develop into a deadly disease that, among other things. manifests itself in a greatly increased leakage in the blood vessels that leads to fluid loss. There is no effective dengue virus vaccine and no specific treatment for patients with dengue fever.

We have studied a large cohort of dengue virus infected patients from outbreaks in Taiwan in 2014 and 2015, and have followed them from the first symptoms to the recovery phase. We found that serum levels of polysaccharide hyaluronan increased very significantly in patients. Hyaluronan is a large linear molecule normally found in connective tissue. We found that serum levels above 70 ng / ml of hyaluronan early in the infection predicted increased risk of developing warning signs, such as severe abdominal pain, bloody vomiting, rapid breathing, and thus severe dengue virus infection. This finding provides access to a biomarker that can be used to identify those patients who should be carefully observed and offered hospital care.

We also found that the viral protein NS1, which is present in large amounts in the serum of infected patients, stimulated the production of hyaluronan in fibroblasts as well as endothelial cells. The increased amount of hyaluronan attracted certain types of immune cells which may contribute to increased inflammation which further increases the production of hyaluronan. In addition, the amount of CD44, a receptor for hyaluronan, decreased on the surface of the endothelial cells after stimulation with NS1. The combination of increased amount of hyaluronan and decreased amount of its receptor affected the contacts between the endothelial cells so that the leak increased. Our findings open an opportunity to treat patients with severe dengue virus infection with inhibitors of hyaluronan, thereby reducing the life-threatening blood vessel leak.

Paraskevi Heldin research group website

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