Mammalian dengue virus receptors

It has been estimated that some 3 billion people live in areas at the risk of infection with the dengue virus, and that up to 100 million infections occur each year, making dengue the most common arthropod-borne viral disease. Humans become infected following the bite of an infected mosquito, and infection can either be essentially without symptoms, or can result in severe, life-threatening manifestations. The initial interaction between a susceptible host cell and the dengue virus is a critical determinant of cell tropism and thus of pathogenicity. As such, considerable effort has been expended on trying to determine the nature of the initial cell: virus interaction and in particular to identify the nature of the receptor proteins used by dengue virus to enter into the cell. Over the last few years a number of proteins, including DC-SIGN, GRP-78, the 37/67kDa high-affinity laminin receptor and heat shock proteins 70 and 90, have all been implicated as dengue virus receptors in a number of cell types. In addition, the specific role of heparan sulfate in dengue virus binding and internalization of dengue still remains to be fully elucidated. This review seeks to provide an overview of the current state of research into mammalian dengue virus receptors, as an increased understanding of which molecules can function as dengue virus receptors and how their expression leads to cell susceptibility will potentially provide novel insights into the pathogenic mechanism of dengue virus infection.