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File photo. The finding is important, according to researchers, as one of the main challenges to make an effective vaccine against dengue is that there are four serotypes or variations of the virus that cause disease. Photo: Bloomberg
File photo. The finding is important, according to researchers, as one of the main challenges to make an effective vaccine against dengue is that there are four serotypes or variations of the virus that cause disease. Photo: Bloomberg

Scientists discover viral protein that makes dengue fatal

The discovery reveals a new potential target for drug and vaccine research

New Delhi: Scientists from University of California, Berkeley have discovered a viral protein vital in making dengue infections fatal, revealing a new potential target for drug and vaccine research. This viral protein is responsible for fluid loss and the resulting shock that make dengue virus infections fatal. There is no available vaccine for dengue which infects more than 390 million people every year.

In a study published in Science Translational Medicine on Wednesday, the team of scientists presented new evidence that a protein secreted by cells infected with the mosquito-borne dengue virus is the prime cause of dengue infections. This protein which is named nonstructural protein NS1, is only one of the 10 viral proteins secreted by infected cells which enter the bloodstream.

The researchers conducted experiments on human lung endothelial cells and in mice and found that blocking this protein in mice protected them from the lethal effects of dengue virus infection. The finding is important, according to researchers, as one of the main challenges to make an effective vaccine against dengue is that there are four serotypes or variations of the virus that cause disease.

According to the study, an initial infection with one of the four serotypes of dengue virus can provide long-term immunity for that specific virus type, but only short-term immunity against the rest. After that, the person is at greater risk for more severe disease from a subsequent infection. Hence, the researchers gave NS1 as a solution as it is produced by all serotypes of dengue virus.

“This is a missing piece in the puzzle of the pathogenesis of dengue," said UC Berkeley professor Eva Harris in a press release. “The role of NS1 itself had been overlooked in severe forms of dengue disease, but we now know that it is an important player. Our findings show that NS1 could be a prime target for drugs, and that it should be considered in vaccine development," added Harris who is a senior author of the study.

Across the world, researchers are struggling to find ways to prevent dengue infections spread by Aedes mosquitoes as public health systems focus on prevention of mosquito breeding and supportive care for patients. According to estimates from the World Health Organization (WHO), roughly half million cases of dengue hemorrhagic fever and dengue shock syndrome occur annually, killing 22,000 people. “What is agonizing is that you don’t know from the outset of an infection who will die," said Harris. “Once the fluid loss begins, it can become fatal in just one to two days," said the molecular virologist.

There are six vaccine candidates against dengue under evaluation in clinical trial, out of which the most advanced candidate vaccine against dengue viruses, called CYD-TDV funded by Sanofi Pasteur, is progressing toward potential registration and review by the WHO in 2016.

“What’s exciting to me is that if we can make antibodies against this toxin and include them in a vaccine, we could potentially prevent a dengue infection from progressing to the more severe symptoms," said study lead author P. Robert Beatty, an assistant research scientist at UC Berkeley’s School of Public Health. “The findings open up new intervention strategies where few now exist," said Beatty in a press release.

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