Newcastle disease virus (NDV) is the model for important, but difficult to study paramyxoviruses like measles, mumps, and respiratory syncytial viruses. It also remains an avian pathogen which produces frequent devastating epizootics in poultry flocks throughout the world. In this proposal we utilize mutants and revertants and monoclonal antibodies to explore NDV's three membrane proteins (HN, F and M); particular emphasis will be placed on HN. These proteins have multiple functions, some of which have been clearly defined and others of which have not. We will attempt to assign protein(s) to functions where this hasn't been done and locate functional areas as well as monoclonal antibody binding sites on the molecules. Using wild type NDV, AV-WT, we will fragment HN, identify peptides and sites of disulfide bonds or glycosylation, and sequence important peptides. Comparing AV-WT and mutant proteins we will map mutations. We will use monoclonal antibodies to these proteins in functional inhibition and peptide binding studies to locate functional areas. We will also use monoclonal antibodies to probe changes in mutant protein binding sites, and in the case of anti-HN antibodies, to select site-specific mutants with alterations in regions important to infectivity. As mutants and antibodies to F become available, we will conduct similar studies on F. Finally, we will conduct additional studies on mutants and revertants to confirm the assignment of group D mutants to the M protein. We will probe previously undetected processing of the HN protein and examine HN's role(s) in hemolysis and infectivity.

Agency
National Institute of Health (NIH)
Institute
National Institute of Allergy and Infectious Diseases (NIAID)
Type
Research Project (R01)
Project #
5R01AI012467-13
Application #
3125198
Study Section
Virology Study Section (VR)
Project Start
1978-09-01
Project End
1993-11-30
Budget Start
1989-12-01
Budget End
1990-11-30
Support Year
13
Fiscal Year
1990
Total Cost
Indirect Cost
Name
University of Massachusetts Medical School Worcester
Department
Type
Schools of Medicine
DUNS #
660735098
City
Worcester
State
MA
Country
United States
Zip Code
01655
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Iorio, R M; Syddall, R J; Glickman, R L et al. (1989) Identification of amino acid residues important to the neuraminidase activity of the HN glycoprotein of Newcastle disease virus. Virology 173:196-204
Iorio, R M; Glickman, R L; Riel, A M et al. (1989) Functional and neutralization profile of seven overlapping antigenic sites on the HN glycoprotein of Newcastle disease virus: monoclonal antibodies to some sites prevent viral attachment. Virus Res 13:245-61
Peeples, M E; Glickman, R L; Gallagher, J P et al. (1988) Temperature-sensitive mutants of Newcastle disease virus altered in HN glycoprotein size, stability, or antigenic maturity. Virology 164:284-9
Glickman, R L; Syddall, R J; Iorio, R M et al. (1988) Quantitative basic residue requirements in the cleavage-activation site of the fusion glycoprotein as a determinant of virulence for Newcastle disease virus. J Virol 62:354-6

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