We don’t hear a whole lot about dengue fever here in the U.S., but it is a really big problem: worldwide, dengue fever strikes roughly 50 million people every year and takes the lives of thousands, but there are currently no specific treatments and no vaccine to prevent infection with the dengue virus. A study published in mBio this week describes a new discovery about how the body fights the dengue virus, a finding that could explain differences in the ability to fight off the virus and help in developing a drug to boost this response. Avirutnan et al. report that a part of the immune system called mannose-binding lectin (MBL) is involved in targeting dengue viruses for destruction. MBL recognizes sugar molecules present on the outsides of many different kinds of viruses and bacteria. When it finds these sugars, MBL can activate the complement system, which targets foreign materials in the body for destruction in any of a number of cruel ways. Scientists have suspected that the complement system may play a role in causing dengue disease, but until now no one knew that it may also be involved in getting rid of the virus and contributing to protection against this infection.
“Before, people thought the complement system was involved primarily in dengue pathogenesis,” says Sujan Shresta, an Associate Professor at the La Jolla Institute for Allergy and Immunology, who reviewed the paper and was not involved in the work. “This paper is the first to look at the role of the complement system in the context of protection” from the dengue virus, says Shresta.
This is an important discovery in terms of human health, says Shresta, because different people naturally make different amounts of MBL. Some people have high levels of MBL, some people have low levels, a fact that may help explain why some individuals are able to fight off the virus while others are not. Individuals with low MBL levels or low MBL activity are more susceptible to variety of other infectious diseases than individuals with high MBL levels or activity.
The authors showed that blood samples with high levels of MBL neutralized dengue more efficiently than samples with lower levels of MBL. This finding suggests that people with high MBL levels in their blood could well be better at fighting dengue infection.
Shresta says this is a clue that could help create therapies for the disease. “You could develop antivirals that work through a similar mechanism,” to deactivate dengue viruses, says Shresta. Vaccines could also be designed to activate this pathway, she says, helping boost the normal functions of the immune system to fight off infection.
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