The University of Nevada, Reno and the Instituto Nacional de Enfermedades Virales Humanas (INEVH) have initiated a collaborative effort to investigate the pathogenesis, ecology and epidemiology of South American Hantaviruses. In our earlier studies we reported the presence of seven novel and phylogenetically distinct hantavirus linages in Argentina. These linages differ at the nucleotide level from 11-21 percent among themselves and 23-26 percent from North American hantaviruses. Three of the linages have been associated with hantavirus pulmonary syndrome and the other with a hemorrhagic fever with renal syndrome. One of the linages (Andes virus) is known to be transmitted directly from humans to humans and a second virus (Oran) is widespread in rodent populations in northern Argentina and is present in 25-40 percent of the native population, as compared to a greater than 1 percent exposure rate throughout Argentina. We propose to determine if the variation in clinical syndromes observed is caused by genetic differences in virus strains or genetic differences in the host. This hypothesis will be tested with the following specific aims: 1) Hantavirus strains associated with a spectrum of clinical syndromes will be examined to identify genetic differences using archived tissue samples, from patients with clinical manifestations varying from a hemorrhagic fever with renal syndrome to a disease resembling hantavirus pulmonary syndrome. 2) A comparison of the pathology of the disease in rodents infected with different hantavirus lineages will be done to determine if the epidemiologic and clinical differences associated with South American hantaviruses is caused by an altered pathogenesis of the viruses in rodents. 3. Identification of neutralizing epitopes in hantavirus glycoproteins: Human monoclonal antibody libraries will be used for the identification and mapping of neutralizing epitopes in both tissue culture and in the rodent reservoir. 4. The pattern of association and co-evolution of South American hantaviruses with their sigmodontine rodent hosts will be identified. 5. Differences in the susceptibility of different human haplotypes to infection with hantaviruses will be determined using archived tissue samples from INEVH. It is anticipated that a clearer understanding of the pathogenesis, ecology and epidemiology of South American hantaviruses will help in the prevention of outbreaks of disease caused by new world hantaviruses.

Agency
National Institute of Health (NIH)
Institute
National Institute of Allergy and Infectious Diseases (NIAID)
Type
Research Project (R01)
Project #
5R01AI045059-05
Application #
6655557
Study Section
Experimental Virology Study Section (EVR)
Program Officer
Cassetti, Cristina
Project Start
1999-09-28
Project End
2005-06-30
Budget Start
2003-07-01
Budget End
2005-06-30
Support Year
5
Fiscal Year
2003
Total Cost
$307,149
Indirect Cost
Name
University of Nevada Reno
Department
Microbiology/Immun/Virology
Type
Schools of Medicine
DUNS #
146515460
City
Reno
State
NV
Country
United States
Zip Code
89557
Rizvanov, Albert A; Khaiboullina, Svetlana F; van Geelen, Albert G M et al. (2006) Replication and immunoactivity of the recombinant Peromyscus maniculatus cytomegalovirus expressing hantavirus G1 glycoprotein in vivo and in vitro. Vaccine 24:327-34
Pearce-Duvet, Jessica M C; St Jeor, Stephen C; Boone, John D et al. (2006) Changes in sin nombre virus antibody prevalence in deer mice across seasons: the interaction between habitat, sex, and infection in deer mice. J Wildl Dis 42:819-24
Deyde, Varough; Rizvanov, Albert; Otteson, Elmer et al. (2005) Identification of a monoclonal antibody from Peromyscus maniculatus (deer mouse) cytomegalovirus (PCMV) which binds to a protein with homology to the human CMV matrix protein HCMV pp71. J Virol Methods 123:9-15
Khaiboullina, Svetlana F; Rizvanov, Albert A; Deyde, Varough M et al. (2005) Andes virus stimulates interferon-inducible MxA protein expression in endothelial cells. J Med Virol 75:267-75
Deyde, Varough M; Rizvanov, Albert A; Chase, Jessica et al. (2005) Interactions and trafficking of Andes and Sin Nombre Hantavirus glycoproteins G1 and G2. Virology 331:307-15
Khaiboullina, Svetlana F; Rizvanov, Albert A; Holbrook, Michael R et al. (2005) Yellow fever virus strains Asibi and 17D-204 infect human umbilical cord endothelial cells and induce novel changes in gene expression. Virology 342:167-76
Khaiboullina, Svetlana F; Morzunov, S P; St Jeor, Stephen C (2005) Hantaviruses: molecular biology, evolution and pathogenesis. Curr Mol Med 5:773-90
Levis, Silvana; Garcia, Jorge; Pini, Noemi et al. (2004) Hantavirus pulmonary syndrome in northwestern Argentina: circulation of Laguna Negra virus associated with Calomys callosus. Am J Trop Med Hyg 71:658-63
Khaiboullina, Svetlana F; Rizvanov, Albert A; Otteson, Elmer et al. (2004) Regulation of cellular gene expression in endothelial cells by sin nombre and prospect hill viruses. Viral Immunol 17:234-51
Rizvanov, Albert A; Khaiboullina, Svetlana F; St Jeor, Stephen (2004) Development of reassortant viruses between pathogenic hantavirus strains. Virology 327:225-32

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