Dengue virus recruits human antibodies to help it infect cells
7 May 2010
The study, which was part-funded by the Wellcome Trust, brings scientists closer to understanding why people who contract dengue fever more than once usually experience more severe and dangerous symptoms the second time around.
The dengue flavivirus, which causes dengue fever, is transmitted by a mosquito bite. The disease is prevalent in sub-tropical and tropical regions including South-east Asia and South America. Symptoms include high fever, severe aching in the joints and vomiting. The virus can also cause hemorrhagic fever, which can be fatal.
Incidence of dengue fever has increased dramatically in the last century and two-fifths of the world's population are now at risk from it, according to the World Health Organization. There are four distinct strains of the virus and no licensed vaccines or drugs have yet been developed to combat any of them.
Now, researchers at Imperial College London have identified a set of antibodies, produced by the human immune system to fight off the dengue virus, that they believe should not be used in the development of any new vaccine to prevent dengue fever. These antibodies - known as precursor membrane protein (prM) antibodies - not only are ineffective at neutralising the virus, but actually help the virus to infect more cells.
The study suggests that when a person who has already been infected with one strain of dengue virus encounters a different strain of dengue virus, the prM antibodies awakened during the first infection spring into action again. However, rather than protecting the body against the second infection, these prM antibodies help the virus to establish itself.
This activity could explain why a second infection with a different strain of the virus can cause more harm than the first infection. The researchers believe that if a dengue virus vaccine contained prM antibodies, this could cause similar problems.
Professor Gavin Screaton, lead author of the study from Imperial College London, said: "A huge proportion of the world’s population is at risk from dengue fever and although treatments have improved, it can be a very unpleasant, painful disease and people are still dying from it. When there is an epidemic of dengue fever, it can put a huge strain on health systems and local economies as well as on individuals and their families.
"Our new research gives us some key information about what is and what is not likely to work when trying to combat the dengue virus. We hope that our findings will bring scientists one step closer to creating an effective vaccine."
The study was conducted by researchers at Imperial College London in the UK and Mahidol University, Khon Kaen Hospital and Songkhla Hospital in Thailand. The work was supported by the Medical Research Council, the Wellcome Trust, the National Institute for Health Research Biomedical Research Centre funding scheme, the Thailand Tropical Disease Research Program T2 and the Thailand National Centre for Genetic Engineering and Biotechnology.
Image: Dengue virus. Credit: AJC1 on Flickr
Reference
Dejnirattisai W et al. Cross-reacting antibodies enhance dengue virus infection in humans. Science 2010 [Epub ahead of print].
