This research application will exploit a newly discovered Hantavirus pulmonary syndrome (HPS) rodent model to discover and test post-exposure prophylactics and therapeutics for treatment of HPS. A brief description of the model is as follows: adult Syrian hamsters injected with Andes virus (ANDV) (a hantavirus that causes the majority of HPS cases in South America) develop a fatal disease that is strikingly similar to the disease in humans (e.g. approximately 2 week incubation period, rapid onset, pulmonary edema, plural effusions, highly lethal). The pathogenesis of HPS in neither humans nor hamsters is understood. Moreover, there are no vaccines or specific drugs to prevent or treat HPS. Broadly speaking, we wish to advance the development of countermeasures to prevent and treat disease caused by ANDV and other highly pathogenic hantaviruses. Here, we will fully characterize the ANDV/hamster HPS model (Aim 1). We will identify viral virulence factors by generating reassortant Hantaviruses and isolating variant viruses (Aim 2). Concurrently, we will test candidate small molecule drugs for a capacity to prevent HPS in the hamster model (Aim 3). Further, we will evaluate the effectiveness of ribavirin in the ANDV/hamster model and examine its potential to cause error catastrophe. When completed, this research will result in a fully characterized HPS rodent model, an understanding of HPS pathogenesis, and insight into the effectiveness of antiviral based counter measures to treat HPS.

Agency
National Institute of Health (NIH)
Institute
National Institute of Allergy and Infectious Diseases (NIAID)
Type
Exploratory/Developmental Grants (R21)
Project #
1R21AI064499-01
Application #
6903150
Study Section
Special Emphasis Panel (ZRG1-IDM-G (90))
Program Officer
Cassetti, Cristina
Project Start
2005-03-03
Project End
2007-02-28
Budget Start
2005-03-03
Budget End
2006-02-28
Support Year
1
Fiscal Year
2005
Total Cost
$336,989
Indirect Cost
Name
Southern Research Institute
Department
Type
DUNS #
006900526
City
Birmingham
State
AL
Country
United States
Zip Code
35205
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Chung, Dong-Hoon; Västermark, Åke; Camp, Jeremy V et al. (2013) The murine model for Hantaan virus-induced lethal disease shows two distinct paths in viral evolutionary trajectory with and without ribavirin treatment. J Virol 87:10997-1007
Ontiveros, Steven J; Li, Qianjun; Jonsson, Colleen B (2010) Modulation of apoptosis and immune signaling pathways by the Hantaan virus nucleocapsid protein. Virology 401:165-78
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