Hantavirus pulmonary syndrome (HPS) is a frequently fatal zoonosis that is endemic in the New World. The virulence of HPS appears to be dependent upon hantaviral genetics. The results of recent studies suggest that the virulence of the New World hantaviruses in Syrian golden hamsters, as in humans, is dependent upon viral genetics. Thus, the hamster model of HPS provides a unique opportunity to elucidate the viral determinants of virulence. The long-term objectives of the proposed research are to 1) elucidate the genetic elements of the hantaviral genome that individually or collectively determine the virulence of the New World hantaviruses, 2) extend our knowledge of the pathogenesis of HPS, 3) identify antiviral compounds for therapy of HPS, and 4) develop vaccines against HPS.
Aim #1 is to develop a plasmid-based genetic system that will enable scientists to map the determinants of virulence to specific elements of the hantaviral genome. Components of the genetic system will be used in future studies to rapidly and economically screen for compounds that can prevent hantaviral infection or disease.
Aim #2 is to rigorously compare and contrast the pathogenicity and virulence of 6 different but genetically very closely related New World hantaviruses.
Aim #3 is to determine the genetic sequences of the complete genomes of these 6 viruses. The genetic sequence database will be used in combination with the experimental animal data from Aim #2 to identify elements of the hantaviral genome that may be causally associated with virulence.
Aim #4 is to assess the contribution of the large, medium, and small segments of the hantaviral genome to the virulence of HPS-like disease in the hamster. The plasmid-based genetic system from Aim #1 will be used to generate reassortant viruses from Maporal virus (MAPV), which is highly virulent in hamsters, and a hantavirus that is not virulent in hamsters and, importantly, that is genetically closely related to MAPV. The results of the work in Aim #4 are expected to narrow the focus of future studies to identify the viral determinants of virulence.
Aim #5 is to investigate the effect of the small, medium, and large genomic segments of MAPV on the evolution of HPS-like disease in hamsters. A series of time-course studies will be done to assess the association between 1) genomic segment, 2) kinetics of viral infection and host response to infection, and 3) virulence. Elements of the viral genome that align with virulence may be appropriate targets for sequence-based antiviral therapy or vaccine development. The plasmid-based genetic system could be used in future studies to develop vaccines to prevent infection or disease and to (in the face of clinical disease) mitigate the severity of HPS. ? ? ?

Agency
National Institute of Health (NIH)
Institute
National Institute of Allergy and Infectious Diseases (NIAID)
Type
Research Project (R01)
Project #
5R01AI067947-03
Application #
7422306
Study Section
Virology - A Study Section (VIRA)
Program Officer
Cassetti, Cristina
Project Start
2006-06-01
Project End
2010-05-31
Budget Start
2008-06-01
Budget End
2009-05-31
Support Year
3
Fiscal Year
2008
Total Cost
$329,932
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
Montoya-Ruiz, Carolina; Cajimat, Maria N B; Milazzo, Mary Louise et al. (2015) Phylogenetic Relationship of NecoclĂ­ Virus to Other South American Hantaviruses (Bunyaviridae: Hantavirus). Vector Borne Zoonotic Dis 15:438-45
Milazzo, Mary Louise; Eyzaguirre, Eduardo J; Fulhorst, Charles F (2014) Pneumonitis in Syrian golden hamsters (Mesocricetus auratus) infected with Rio Mamoré virus (family Bunyaviridae, genus Hantavirus). Virus Res 191:39-44
Cajimat, Maria N B; Milazzo, Mary Louise; Bradley, Robert D et al. (2012) Ocozocoautla de espinosa virus and hemorrhagic fever, Mexico. Emerg Infect Dis 18:401-5
Milazzo, Mary L; Cajimat, Maria N B; Romo, Hannah E et al. (2012) Geographic distribution of hantaviruses associated with neotomine and sigmodontine rodents, Mexico. Emerg Infect Dis 18:571-6
Cajimat, Maria N B; Milazzo, Mary Louise; Haynie, Michelle L et al. (2011) Diversity and phylogenetic relationships among the North American Tacaribe serocomplex viruses (family Arenaviridae). Virology 421:87-95
Milazzo, Mary L; Cajimat, Maria N B; Duno, Gloria et al. (2011) Transmission of Guanarito and Pirital viruses among wild rodents, Venezuela. Emerg Infect Dis 17:2209-15
Hanson, John Delton; Utrera, Antonio; Fulhorst, Charles F (2011) The delicate pygmy rice rat (Oligoryzomys delicatus) is the principal host of Maporal virus (family Bunyaviridae, genus Hantavirus). Vector Borne Zoonotic Dis 11:691-6
Richter, Martin H; Hanson, John Delton; Cajimat, Maria N et al. (2010) Geographical range of Rio Mamore virus (family Bunyaviridae, genus Hantavirus) in association with the small-eared pygmy rice rat (Oligoryzomys microtis). Vector Borne Zoonotic Dis 10:613-20
Billings, Adrian N; Rollin, Pierre E; Milazzo, Mary L et al. (2010) Pathology of Black Creek Canal virus infection in juvenile hispid cotton rats (Sigmodon hispidus). Vector Borne Zoonotic Dis 10:621-8
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

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