The objectives of this research proposal are (1) to develop a rapid and easy-to-use nucleic acid diagnostic test to detect hantaviruses in blood, plasma, or serum of infected individuals and carrier rodents, (2) to develop a rapid diagnostic test to detect hantavirus antibodies in blood, plasma, or serum of infected individuals, (3) to develop a hantavirus nucleic acid discriminatory test, (4) to develop TaqMan-based quantitative assays to estimate hantavirus load in virus infected samples, (5) to develop a flow cytometry assay to detect Sin Nombre virus (SNV) antigen in peripheral blood mononuclear cells (PBMC) of patients with hantavirus cardiopulmonary syndrome (HCPS), (6) to develop inbred sublines of fully homozygous deer mice, and (7) to establish tools to dissect deer mouse cellular immune responses to hantavirus infection. The hantavirus nucleic acid and antibody diagnostic tests should be able to yield results in less than one hour, and will assist in the early detection and follow up of hantavirus infections. The availability of the hantavirus nucleic acid discriminatory assay will allow identification of specific viral isolates involved in hantavirus outbreaks and their possible origins. Methods to accurately quantitate hantavirus load in human patients or in animal models, along with the availability of a flow cytometry-based SNV assay, inbred homozygous deer mice, and methodologies to dissect the deer mouse cellular immune responses to hantavirus will facilitate better understanding, prevention, and treatment of hantavirus infections. This research involves collaborative efforts between Chiron Corporation and the School of Medicine, University of New Mexico. A previous collaboration between the two organizations was initiated in 1994 but discontinued in 1997 when Chiron Corporation withdrew funding for hantavirus diagnostic research, as there was no strategic fit at that time. The information generated from the studies proposed in this task will be crucial for the rapid identification of possible bioterrorism attacks involving hantavirus agents and will be vital to assist the medical and public health organizations to efficiently respond to hantavirus outbreaks and/or threats.

Agency
National Institute of Health (NIH)
Institute
National Institute of Allergy and Infectious Diseases (NIAID)
Type
Research Project--Cooperative Agreements (U01)
Project #
5U01AI054779-05
Application #
7169822
Study Section
Special Emphasis Panel (ZAI1-ALR-M (J1))
Program Officer
Cassetti, Cristina
Project Start
2003-07-15
Project End
2007-12-31
Budget Start
2007-01-01
Budget End
2007-12-31
Support Year
5
Fiscal Year
2007
Total Cost
$964,654
Indirect Cost
Name
Novartis Vaccines and Diagnostics, Inc.
Department
Type
DUNS #
046866463
City
Cambridge
State
MA
Country
United States
Zip Code
02139
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Prescott, Joseph B; Hall, Pamela R; Bondu-Hawkins, Virginie S et al. (2007) Early innate immune responses to Sin Nombre hantavirus occur independently of IFN regulatory factor 3, characterized pattern recognition receptors, and viral entry. J Immunol 179:1796-802

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