A VIRUS RECEPTOR IDENTIFIED
A cell receptor decisive for infection by the dengue virus , which many research teams throughout the world had been seeking for a long time, has just been identified by two teams at the Institut Pasteur. This work, published in EMBO Reports, is a major step toward understanding this infection, which affects 60 to 100 million people each year throughout the world. This observation may pave the way for the development of specific treatments that do not yet exist.
The dengue virus infects humans when an infected Aedes aegypti mosquito feeds on their blood. Once inoculated in the skin, the virus interacts with certain cells of the immune system of that are present locally, called dendritic cells, considered to be the first cells targeted by the virus. It was precisely on the surface of these cells that the teams led by Philippe Desprès, in the Flavivirus-Host Molecular Interactions Unit, and Jean-Louis Virelizier and Fernando Arenzana, in the Viral Immunology Unit, demonstrated the role of dengue virus receptor played by a molecule known as DC-SIGN. Identifying this essential receptor, which becomes involved in the process at the initial stages of infection by dengue virus, raises hope for better understanding and blocking the infection.
Dendritic cells capture and disseminate antigens throughout the organism after DC-SIGN receptor interaction with protein antigens. Mosquitoes inject the dengue virus , whose envelope proteins the insect has modified by adding certain sugars (glycosylation) , into the dermis and , therefore, in direct contact with the local dendritic cells. The researchers at the Institut Pasteur demonstrated that recognition of the glycosylated viral envelope by the DC-SIGN receptor is necessary for infection of dendritic cells to occur. In particular, they showed that monoclonal antibodies to DC-SIGN , or a soluble form of DC-SIGN, reduces by over 90% infection of the dendritic cells by the dengue virus produced by mosquito cells. Furthermore, the researchers made other types of cells permissive to the infection by making them express DC-SIGN on their surfaces.
Although these results still have to be confirmed in vivo, they represent significant progress in the understanding of what is probably a key step in the infection and propagation of the dengue virus in its human host and of the immuno-pathogenesis of this infection. This work also reveals a potential target for treatment.
It should be recalled that 250 million people live in regions where there is a risk of dengue transmission (tropical regions) and that the serious form of the disease, dengue hemorragic fever, is on the rise throughout the world, particularly in Latin America and the Caribbean.
ICAM3-grabbing non-integrin is essential for the productive infection of human
dendritic cells by mosquito-cell-derived dengue viruses" - EMBO reports,
Vol. 4, #7, 2003
Erika Navarro-Sanchez (1), Ralf Altmeyer (2), Ali Amara (2), Olivier Schwartz (3), Franck Fieschi (4), Jean-Louis Virelizier (2), Fernando Arenzana-Seisdedos (2) and Philippe Desprès (1)
1 Flavivirus-Host Molecular
Interactions Unit, Institut Pasteur, Paris
2 Viral Immunology Unit, Institut Pasteur, Paris
3 Virus and Immunity Laboratory, Institut Pasteur, Paris
4 Structural Biology Institute, CEA-CNRS-UJF, UMR 5075, Grenoble
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