Previous work suggests that neutralization of Newcastle disease virus (NDV) by a panel of monoclonal antibodies (MAbs) specific for its HN glycoprotein requires the addition of MAbs to four sites having different functional inhibition properties. The long-term objective is a better understanding of the basis for this phenomenon and its relevance to the mechanism of neutralization of pleiomorphic enveloped viruses. Specifically, the proposal is aimed at the construction of """"""""neutralization map"""""""" of the NDV HN glycoprotein, relating certain domains of the molecule to specific mechanisms of neutralization and possibly to site-specific efficiencies of neutralization. This will be accomplished by determination of the amino acid sequence of the HN of nonneutralizable antigenic variants selected with MAbs to several epitopes on the glycoprotein in conjunction with studies of the mechanism(s) by which these MAbs neutralize viral infectivity. This will make it possible to correlate different mechanisms and efficiencies of neutralization with specific HN sequences.
Other aims i nclude the characterization of the persistent fraction of nonneutralized virus and its interaction with the host cell. The possible role of the pleiomorphism typical of paramyxoviruses in the estasblishment of persistent fractions will be investigated. Also, the interaction of the virus-MAb complex with the host cell will be contrasted to that of the untreated virus. Each of these approaches will address a different aspect of the phenomenon which, in turn, will add to our overall understanding of the mechanism of neutralization of this group of viruses.

Agency
National Institute of Health (NIH)
Institute
National Institute of Allergy and Infectious Diseases (NIAID)
Type
First Independent Research Support & Transition (FIRST) Awards (R29)
Project #
5R29AI024770-03
Application #
3454103
Study Section
Virology Study Section (VR)
Project Start
1987-04-01
Project End
1992-03-31
Budget Start
1989-04-01
Budget End
1990-03-31
Support Year
3
Fiscal Year
1989
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