Viruses such as measles, influenza, and HIV cause considerable morbidity worldwide. New emerging viruses are a constant threat because of the speed of their spread and their potential to cause widespread disease before therapies can be developed. Not much is known about innate immune responses against viruses. The immune signaling pathways in Drosophila are highly conserved with immune pathways in humans, worms, and plants, making it an excellent model for study. We have established a system to examine antiviral innate immune responses using the dsRNA birnavirus, Drosophila X virus (DXV) infection of Drosophila melanogaster. We have identified the Toll and RNAi pathways as important for host defense. From a forward genetic screen, we have also identified novel mutations important for viral pathogenesis or the antiviral immune response.
The specific aims of this proposal are: 1. To determine whether the new DXV-susceptible mutants are acting in the Toll, RNAi, or JAK/STAT pathways. 2. To study how an overactive immune response can be damaging to the host. An overactive immune response appears to be harmful to the fly during DXV infection. We will determine the possible role of the Toll pathway in this response and characterize the DXV-resistant mutants to potentially identify negative regulators of this pathway. 3. To identify by map-based positional cloning two novel antiviral genes that affect either the Toll or RNAi pathway. Overall, the proposed experiments may give insight to new pathways, or new genes in Toll or RNAi pathways that are important for antiviral immune responses.

Public Health Relevance

Viruses come in many varieties and are successful in causing disease in humans;the Toll pathway and RNA interference (RNAi) are two means that the host uses to combat viral infection. We will identify novel genes important for the antiviral immune response and determine if they are affecting these two pathways.

Agency
National Institute of Health (NIH)
Institute
National Institute of Allergy and Infectious Diseases (NIAID)
Type
Research Project (R01)
Project #
5R01AI076564-02
Application #
7628085
Study Section
Immunity and Host Defense Study Section (IHD)
Program Officer
Cassetti, Cristina
Project Start
2008-06-01
Project End
2010-05-31
Budget Start
2009-06-01
Budget End
2010-05-31
Support Year
2
Fiscal Year
2009
Total Cost
$337,500
Indirect Cost
Name
University of MD Biotechnology Institute
Department
Type
Organized Research Units
DUNS #
603819210
City
Baltimore
State
MD
Country
United States
Zip Code
21202
Garg, Aprajita; Wu, Louisa P (2014) Drosophila Rab14 mediates phagocytosis in the immune response to Staphylococcus aureus. Cell Microbiol 16:296-310
Gonzalez, Elizabeth A; Garg, Aprajita; Tang, Jessica et al. (2013) A glutamate-dependent redox system in blood cells is integral for phagocytosis in Drosophila melanogaster. Curr Biol 23:2319-2324