The applicant plans to continue studies aimed at understanding at a molecular level the pathogenesis of reovirus infections in mice. This will entail looking at the nature of reovirus interactions with the heart to develop a workable model of viral induced myocarditis. We will examine the liver and biliary tract to see if reovirus is excreted into the bile. Mutants in the hemagglutinin of reovirus 1 will be generated to study the pathogenesis of T1 infection. We will attempt to identify the genetic basis for difference in lethality of reovirus 3 by peripheral inoculation as compared to direct CNS inoculation. We will study interferon to determine if differences in induction of interferon in vitro explain certain differences in viral virulence following P.O. inoculation. Studies will be performed on cell cultures to determine the mechanism of neutralization of reovirus 1 and 3. In addition we will analyze the movement of reovirus into endosomes to understand what regulates early events in reovirus infection. We will study reoviruses in normal and transformed cells to determine how oncogenes alter the growth cycle of reoviruses. Lastly we will continue to sequence genes playing a role in viral virulence as well as biological variants in these genes. These studies should help explain some of the in vivo phenomenon in molecular detail.

Agency
National Institute of Health (NIH)
Institute
National Institute of Allergy and Infectious Diseases (NIAID)
Type
Method to Extend Research in Time (MERIT) Award (R37)
Project #
5R37AI013178-18
Application #
3480733
Study Section
Special Emphasis Panel (NSS)
Project Start
1976-06-30
Project End
1996-05-31
Budget Start
1993-06-01
Budget End
1994-05-31
Support Year
18
Fiscal Year
1993
Total Cost
Indirect Cost
Name
Harvard University
Department
Type
Schools of Medicine
DUNS #
082359691
City
Boston
State
MA
Country
United States
Zip Code
02115
Derrien, Muriel; Hooper, Jay W; Fields, Bernard N (2003) The M2 gene segment is involved in the capacity of reovirus type 3Abney to induce the oily fur syndrome in neonatal mice, a S1 gene segment-associated phenotype. Virology 305:25-30
Derrien, M; Fields, B N (2000) Anti-interleukin-3 and anti-nerve growth factor increase neonatal mice survival to reovirus type 3 clone 9 per oral challenge. J Neuroimmunol 110:209-13
Derrien, M; Fields, B N (1999) Reovirus type 3 clone 9 increases interleukin-1alpha level in the brain of neonatal, but not adult, mice. Virology 257:35-44
Dryden, K A; Farsetta, D L; Wang, G et al. (1998) Internal/structures containing transcriptase-related proteins in top component particles of mammalian orthoreovirus. Virology 245:33-46
Luongo, C L; Dryden, K A; Farsetta, D L et al. (1997) Localization of a C-terminal region of lambda2 protein in reovirus cores. J Virol 71:8035-40
Hooper, J W; Fields, B N (1996) Role of the mu 1 protein in reovirus stability and capacity to cause chromium release from host cells. J Virol 70:459-67
Morin, M J; Warner, A; Fields, B N (1996) Reovirus infection in rat lungs as a model to study the pathogenesis of viral pneumonia. J Virol 70:541-8
Wilson, G A; Morrison, L A; Fields, B N (1994) Association of the reovirus S1 gene with serotype 3-induced biliary atresia in mice. J Virol 68:6458-65
Morin, M J; Warner, A; Fields, B N (1994) A pathway for entry of reoviruses into the host through M cells of the respiratory tract. J Exp Med 180:1523-7
Rozinov, M N; Fields, B N (1994) Interference following mixed infection of reovirus isolates is linked to the M2 gene. J Virol 68:6667-71

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