Project Information
Dengue Virus Classification
Group: Group IV ((+)ssRNA, no DNA stage)
- Family: Flaviviridae
- Genus: Flavivirus
- Species: Dengue Virus
Significance
Dengue virus (DEN), a category-A pathogen, is a significant threat to public health world wide. The virus is transmitted to humans by the mosquitoes Aedes aegypti and Ae. albopictus. The incidence of dengue fever (DF), dengue hemorrhagic fever (DHF), and dengue shock syndrome (DSS) are rapidly increasing, and more than 2.5 billion people live in regions endemic for the disease. Presently approximately 50-100 million cases of DF occur yearly with more than 500,000 resulting in severe and potentially fatal forms of the disease (DHF & DSS). Several factors contribute to the threat posed by dengue. Most significant are lack of cross-reactive immunity for the four DEN serotypes (DEN-1, DEN-2, DEN-3, and DEN-4), hyperendemic circulation of the four different serotypes in the same geographical area, frequent worldwide travel, high population density, and lack of effective mosquito control programs. Other socioeconomic factors only amplify the challenge of dengue control.
Genomic Global Population Structure and Disease Outcome Project
Despite the threat of Dengue virus to public health and its importance to research on viral hemorrhagic fevers our understanding of the virulence, pathogenesis, and mechanisms of re-emergence of the dengue virus is limited. As a consequence, presently no vaccine or anti-viral therapy exists for this flavivirus, and the genetic underpinnings of disease outcomes are unknown. Studies of nucleotide divergence among he different serotypes has largely been limited to a single gene. This lack of basic information of viral diversity severely limits vaccine and anti-viral therapy development efforts. In addition, the presence of immune pathology in secondary DEN infections indicates that previous non-sterile immune response to one serotype can exacerbate the immune response to the secondary infections caused by another serotype. This host-viral interaction also represents a considerable challenge for vaccine development.
Through this project intend to sequence >3500 dengue genomes of distinct geographic origin and disease to build the genomic infrastructure needed to study and combat this virus. We will define the population structure of the virus at multiple scales (i.e. within host, local, regional, and continental) which will enable determination of the impact of introduced strains versus indigenous evolution on disease outcomes. Additionally, this project aims to understand the genomic correlates of disease severity and will provide the first map of genomic distributions with reference to DF, DHF, and DSS.
This project is supported by the NIAID funded Broad Institute Microbial Sequencing Center.
Principal Collaborators: Genome Resources in Dengue Consortium (GRID)
Photo Credits and Captions
The images on the home page are, from left to right:
- Photo of Aedes Aegypti from the CDC's Public Health Image Library; photographer: Jim Gathany.
- mature Dengue-2 virus particles replicating in five-day-old tissue culture cells. Electron micrograph, CDC
- This image shows the immature dengue particle. Notable are the 60 protein "spikes" which jut from the surface, making the immature particle far less smooth than the mature form. One spike is circled for reference. Knowledge of how the immature particle develops into the mature, infectious dengue virus could be important to developing antiviral medicines. (Purdue Structural Virology)
- The structure of the mature dengue virus particle was determined in 2002 by Michael Rossmann and Richard Kuhn's team. The virus' surface is unusually smooth and its membrane is completely enclosed by a protein shell. The protein is color-coded blue, green and yellow to show the three specific domains of the protein. The protein shell serves as a cage for the genetic material inside. (Purdue Structural Virology)
- An image of the dengue virus, based on cryoelectron microscopy and image reconstruction (Purdue Structural Virology)
