How dengue virus enters cells found

Scientists have unveiled the mechanism behind how dengue enters cells of our immune system, a finding that could help develop vaccine for the deadly virus.

Dengue fever, an infectious tropical disease caused by a mosquito-borne virus, afflicts millions of people each year, causing fever, headache, muscle and joint pains and a characteristic skin rash, researchers said. In some people the disease progresses to a severe, often fatal, form known as dengue hemorrhagic fever.

Despite its heavy toll, the prevention and clinical treatment of dengue infection has been a “dramatic failure in public health compared to other infectious diseases like HIV,” said Ping Liu of the University of North Carolina at Chapel Hill.

Now, new research by Liu and her colleagues could offer vital insight into the mechanism of dengue virus entry into cells – and aid vaccine and clinical drug development. Liu along with dengue fever expert Aravinda de Silva, used high-resolution microscopes to examine the expression of a particular protein, known as DC-SIGN, on the surface of immune system cells called dendritic cells.

The normal role of DC-SIGN (dendritic cell-specific intercellular adhesion molecule grabbing nonintegrin) is to capture pathogens so that fragments of those pathogens can be presented as antigens on the surface of the dendritic cells.

Such antigens then are recognised by T cells – the workhorse cells of the immune system – “which is one of the first steps in the normal immune response,” Liu said. While it has been known for some time that dengue used DC-SIGN to attach to cells, Liu and her colleagues used high-resolution microscopy to study exactly how the viruses used the protein to gain entry into cells.
“DC-SIGN has a unique carbohydrate recognition domain on its extracellular portion, which binds to all sorts of carbohydrates on pathogens,” she said.

“An effective medication or vaccine should stop the process of dengue virus entry into cells,” Liu said. She said, de Silva and his colleagues have identified strong neutralisation antibodies that block dengue infection. By identifying the mechanism of antibody neutralisation, Liu and colleagues hope to advance the development of vaccines for dengue virus infections.

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