Dengue virus (DV) causes dengue fever (DF) and dengue hemorrhagic fever/dengue shock Syndrome (DHF/DSS), the most prevalent arthropod-borne viral illness in humans worldwide. Both clinical and in vitro laboratory studies have implicated immune-based mechanisms for the manifestations of DHF. Due to the lack of an adequate animal model for DV infection, the immunopathogenic mechanisms of DHF are not yet fully elucidated. As a first step towards understanding the role of the immune system in DV infection in vivo. this proposal aims to optimize a mouse model for DV infection by systematically evaluating novel routes of infection, different viral and mouse strains, and co-injection of immunomodulatory compounds (Specific Aim 1). Since the chemokine network is important in orchestrating anti-viral immune responses and evidence supports a role for chemokines in the immunopathogenesis of DHF, we hypothesize that chemokines (particularly CCL5) participate in the clearance of virus in mice challenged with DV. Thus, Specific Aim 2 is to define the in vivo expression pattern and function of CCL5 in mice with primary DV infections. The long-term goal of this work is to examine the contribution of chemokines to the immunopathogenesis of DHF in vivo.

Agency
National Institute of Health (NIH)
Institute
National Institute of Allergy and Infectious Diseases (NIAID)
Type
Postdoctoral Individual National Research Service Award (F32)
Project #
1F32AI051070-01
Application #
6445297
Study Section
Experimental Virology Study Section (EVR)
Program Officer
Meegan, James M
Project Start
2002-05-03
Project End
Budget Start
2002-05-03
Budget End
2003-05-02
Support Year
1
Fiscal Year
2002
Total Cost
$48,148
Indirect Cost
Name
University of California Berkeley
Department
Internal Medicine/Medicine
Type
Schools of Public Health
DUNS #
094878337
City
Berkeley
State
CA
Country
United States
Zip Code
94704