Dengue virus (DENV) is the most prevalent mosquito-borne virus causing disease in humans, with an estimated 2.5 billion people at risk of DENV infection, resulting in about 390 million annual infections worldwide. There are currently no licensed vaccines or specific therapeutics, and the death rate for severe dengue without proper supportive care can be over 20%. There are no immune competent animal models for dengue disease, which has made immune pathogenesis studies very challenging. The overall objective of this application is to develop a novel ex vivo human tonsil histoculture system to study DENV infection in the context of whole lymphoid tissue cytoarchitecture. In preliminary studies, we have demonstrated that human tonsil histocultures support a productive infection of WT DENV-2. By optimizing this histoculture system, we will work toward achieving our long-term goal of characterizing the infection of the all four serotypes of DENV in human tonsil histocultures, in which we can study the cell tropism, infection kinetics and immune responses of DENV in a more physiological context than existing cell-based systems.

Public Health Relevance

Dengue Virus (DENV) is the most prevalent arbovirus causing disease in millions of people worldwide. There are currently no licensed vaccines or specific therapeutics, and the death rate for severe dengue without proper supportive care can be over 20%. We propose to develop an ex vivo human tonsil histoculture system to study DENV by recapitulating early events in DENV infection and to test potential therapeutics and vaccine candidates.

Agency
National Institute of Health (NIH)
Institute
National Institute of Allergy and Infectious Diseases (NIAID)
Type
Exploratory/Developmental Grants (R21)
Project #
5R21AI116022-02
Application #
8974272
Study Section
Special Emphasis Panel (ZRG1)
Program Officer
Challberg, Mark D
Project Start
2014-12-01
Project End
2016-11-30
Budget Start
2015-12-01
Budget End
2016-11-30
Support Year
2
Fiscal Year
2016
Total Cost
Indirect Cost
Name
Icahn School of Medicine at Mount Sinai
Department
Microbiology/Immun/Virology
Type
Schools of Medicine
DUNS #
078861598
City
New York
State
NY
Country
United States
Zip Code
10029
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