The studies that are planned are directed toward the understanding of the mechanism of persistent viral infection in cell culture model systems using vesicular stomatitis, influenza type A, and Newcastle disease viruses. Special emphasis will be placed on analysis of the evolution of virus and host cells during long-term persistent infections. The information obtained may have pertinence to human illnesses which involve persistent viral infections. The importance of such diseases is being increasingly recognized. Investigations will be continued dealing with the mechanism of action of interferon. Particular emphasis will be placed on characterization of an effect of interferon recently discovered in this laboratory, namely, inhibition of cellular endocytosis and virus uptake. This effect of interferon is potentially relevant to the use of interferon as an antiviral and antitumor agent. In addition, the first example of a virus activity which can overcome an interferon-induced function (i.e., double-stranded RNA-dependent protein kinase) will be investigated and characterized. Besides evaluating the role of the interferon-induced protein kinase in interferon-mediated restriction of viral protein synthesis, these studies may provide insight into the mechanism of eukaryotic protein synthesis and its alteration by virus infection. The mechanism of virus-mediated inhibition of endocytosis and superinfection exclusion will be further investigated. These studies will yield valuable information concerning the influence of viral infection on host cell plasma membrane function and on the mechanism of entry of virus into cells.

Agency
National Institute of Health (NIH)
Institute
National Institute of Allergy and Infectious Diseases (NIAID)
Type
Research Project (R01)
Project #
5R01AI006264-24
Application #
3124288
Study Section
Virology Study Section (VR)
Project Start
1974-09-01
Project End
1989-08-31
Budget Start
1987-09-01
Budget End
1988-08-31
Support Year
24
Fiscal Year
1987
Total Cost
Indirect Cost
Name
University of Pittsburgh
Department
Type
Schools of Medicine
DUNS #
053785812
City
Pittsburgh
State
PA
Country
United States
Zip Code
15213
Youngner, J S; Treanor, J J; Betts, R F et al. (1994) Effect of simultaneous administration of cold-adapted and wild-type influenza A viruses on experimental wild-type influenza infection in humans. J Clin Microbiol 32:750-4
Maloy, M L; Whitaker-Dowling, P; Youngner, J S (1994) Dominance of cold-adapted influenza A virus over wild-type viruses is at the level of RNA synthesis. Virology 205:44-50
Lucas, W T; Youngner, J S (1992) The use of hybrid-selected template increases the specificity of the polymerase chain reaction. PCR Methods Appl 2:41-4
Whitaker-Dowling, P; Maassab, H F; Youngner, J S (1991) Dominant-negative mutants as antiviral agents: simultaneous infection with the cold-adapted live-virus vaccine for influenza A protects ferrets from disease produced by wild-type influenza A. J Infect Dis 164:1200-2
Whitaker-Dowling, P; Zvolenski, R; Youngner, J S (1991) The genes associated with trans-dominance of the influenza A cold-adapted live virus vaccine. Virology 180:81-7
Simon, K O; Whitaker-Dowling, P A; Youngner, J S et al. (1990) Sequential disassembly of the cytoskeleton in BHK21 cells infected with vesicular stomatitis virus. Virology 177:289-97
Lancz, G; Whitaker-Dowling, P; Marsh, Y V et al. (1990) Inhibition of vesicular stomatitis virus replication in dexamethasone-treated L929 cells. Proc Soc Exp Biol Med 193:190-6
Simon, K O; Cardamone Jr, J J; Whitaker-Dowling, P A et al. (1990) Cellular mechanisms in the superinfection exclusion of vesicular stomatitis virus. Virology 177:375-9
Whitaker-Dowling, P; Lucas, W; Youngner, J S (1990) Cold-adapted vaccine strains of influenza A virus act as dominant negative mutants in mixed infections with wild-type influenza A virus. Virology 175:358-64
Jordan, J A; Whitaker-Dowling, P; Youngner, J S (1989) The L protein of a VSV mutant isolated from a persistent infection is responsible for viral interference and dominance over the wild-type. Virology 169:137-41

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