Pathogenesis and prevention of dengue virus infection: state-of-the-art

The spread of dengue (DEN) worldwide combined with an increased severity of the DEN-associated clinical outcomes has made this mosquito-borne virus of great global public health importance. This article reviews the latest findings in the field of DEN pathogenesis, vector control and vaccine development.

Atypical clinical manifestations as well as a shift in the age of DEN-infected patients have forced a revisit of the current definitions and classifications of the DEN-associated diseases. The antibody-mediated internalization of DEN virus triggers intracellular pathways that further enhance viral replication and output. A correlation between the human leukocyte antigen system and disease severity was found. The development of tetravalent DEN vaccine candidates is reaching its final stages, though the antibody levels required to protect against the four DEN serotypes are still unknown.

Efforts have been devoted to identify the host target cells that are permissive or resistant to DEN virus replication and to decipher the downstream events that would result in either disease enhancement or protection. Strong emphasis has recently been made on genetic polymorphisms that confer DEN protection versus susceptibility to severe DEN. The increasing knowledge gained from basic science should help to better design effective DEN vaccines.