Hantavirus cardiopulmonary syndrome (HCPS) is a frequently fatal zoonosis that is endemic in the Americas. Andes virus (ANDV) and other Hantaviruses that cause HCPS are NIAID Priority Pathogens (Category C). Laboratory models of HCPS are needed to elucidate the pathogenesis of HCPS and to rigorously assess the efficacy of candidate therapies for the disease. The broad objective of this application is to extend and refine our knowledge of the pathogenesis of hantaviral infections in rodent models of HCPS.
The first aim of this application is to characterize the course of ANDV infection in the hamster (particularly the pathophysiological events that precede or coincide with lethal outcome), assess the effect of ANDV infection in the hamster heart, and determine whether ANDV is substantively more lethal than Maporal virus in the hamster. A substantial difference in lethality between the viruses will be used in future studies to elucidate the viral determinants of the virulence of hantaviral infections in hamster models of human disease.
The second aim i s to assess the role of inducible nitric oxide synthase in the pathogenesis of HCPS-like disease in the laboratory mouse. The results of a preliminary study suggest that the vigorous oxidative response in infected lung and heart tissues is a critical deterrent to the progression of HCPS-like disease in laboratory mice. A series of studies will be done to test the pathogenicity and virulence of ANDV and MAPV each in knockout mice deficient in inducible nitric oxide synthase. A mouse model of severe or lethal HCPS could substantively augment studies on the pathogenesis of the capillary leak that results in the life-threatening pulmonary edema HCPS.

Agency
National Institute of Health (NIH)
Institute
National Institute of Allergy and Infectious Diseases (NIAID)
Type
Exploratory/Developmental Grants (R21)
Project #
5R21AI063235-02
Application #
7025671
Study Section
Special Emphasis Panel (ZRG1-IDM-G (90))
Program Officer
Cassetti, Cristina
Project Start
2005-03-15
Project End
2009-01-31
Budget Start
2006-03-01
Budget End
2009-01-31
Support Year
2
Fiscal Year
2006
Total Cost
$294,903
Indirect Cost
Name
University of Texas Medical Br Galveston
Department
Pathology
Type
Schools of Medicine
DUNS #
800771149
City
Galveston
State
TX
Country
United States
Zip Code
77555
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Milazzo, Mary L; Duno, Gloria; Utrera, Antonio et al. (2010) Natural host relationships of hantaviruses native to western Venezuela. Vector Borne Zoonotic Dis 10:605-11
Eyzaguirre, Eduardo J; Milazzo, Mary Louise; Koster, Frederick T et al. (2008) Choclo virus infection in the Syrian golden hamster. Am J Trop Med Hyg 78:669-74