People living in Sri Lanka have started to experience large epidemics of dengue hemorrhagic fever (DHF) after 1989. Previous studies from our group indicate that a genetic change in circulating DEN serotype 3 (DEN3) viruses is responsible for the emergence of DHF in Sri Lanka. DEN3 viruses from Sri Lanka are very closely related and belong to genotype III but isolates from before and after the emergence of DHF are genetically distinct. In this proposal we plan cell culture experiments to identify phenotypic differences between DEN3 strains associated with servere and mild disease. Specifically we plan to test two hypotheses about dengue strains and disease severity. The first hypothesis is that post DHF DEN3 isolates are inherently more virulent and are able to infect human cells better than the pre DHF isolates. To test this hypothesis we plan to compare the ability of DEN3 strains to infect and replicate in human monocytes/macrophages and hepatocyte cell lines. The second hypothesis is that pre-exisitng dengue antibody in the population neutralizes the preDHF DEN3 isolates better than the post DHF isolates. We propose to test this hypothseis by comparing the ability of antisera from people with previous dengue infections to neutralize the pre and post DHF DEN3 isolates. These studies will pinpont key differences between DEN3 strains, which may be responsible for variations in human disease severity.

Agency
National Institute of Health (NIH)
Institute
National Institute of Allergy and Infectious Diseases (NIAID)
Type
Predoctoral Individual National Research Service Award (F31)
Project #
5F31AI058923-02
Application #
6893713
Study Section
Special Emphasis Panel (ZRG1-MBC-1 (29))
Program Officer
Hernandez, Milton J
Project Start
2004-05-01
Project End
2007-04-30
Budget Start
2005-05-01
Budget End
2006-04-30
Support Year
2
Fiscal Year
2005
Total Cost
$27,089
Indirect Cost
Name
University of North Carolina Chapel Hill
Department
Microbiology/Immun/Virology
Type
Schools of Medicine
DUNS #
608195277
City
Chapel Hill
State
NC
Country
United States
Zip Code
27599