The paramyxoviruses are important respiratory pathogens of both adults and children. The major cytopathic effect in paramyxovirus-infected cells is the formation of multi-nucleate syncytia. This is mediated by membrane fusion, induced by the two viral surface glycoproteins. One can identify many similarities between paramyxovirus fusion and those of other viruses, such as the influenza and human immunodeficiency viruses. However, unlike the other viruses, the paramyxovirus receptor recognition and fusion-promoting activities reside on two different surface glycoprotein spike structures, the attachment and fusion proteins, respectively. The long-term goal of our research has been to understand the early interactions of the paramyxovirus glycoproteins with the cell surface. The attachment and fusion proteins, once thought to be independent, have now been shown to take part in a specific interaction that is obligatorily linked to the conversion of the latter to its fusion-active form. The objective of this proposal is to understand the mechanism of formation of the complex between the two proteins and how this complex functions in the fusion process. Specific aspects of complex formation that will be elucidated include the role of receptor recognition by the terminal globular domain of the attachment protein, the changes this protein must undergo to take part in the interaction with the fusion protein and the sites on both proteins that mediate the interaction. This information will help elucidate how these important pathogens gain entry into, and spread between, cells, possibly identifying new anti-viral strategies for their control.

Agency
National Institute of Health (NIH)
Institute
National Institute of Allergy and Infectious Diseases (NIAID)
Type
Research Project (R01)
Project #
5R01AI049268-05
Application #
6866433
Study Section
Virology Study Section (VR)
Program Officer
Kim, Sonnie
Project Start
2001-04-01
Project End
2006-03-31
Budget Start
2005-04-01
Budget End
2006-03-31
Support Year
5
Fiscal Year
2005
Total Cost
$354,800
Indirect Cost
Name
University of Massachusetts Medical School Worcester
Department
Genetics
Type
Schools of Medicine
DUNS #
603847393
City
Worcester
State
MA
Country
United States
Zip Code
01655
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Mirza, Anne M; Iorio, Ronald M (2013) A mutation in the stalk of the newcastle disease virus hemagglutinin-neuraminidase (HN) protein prevents triggering of the F protein despite allowing efficient HN-F complex formation. J Virol 87:8813-5
Mahon, Paul J; Mirza, Anne M; Iorio, Ronald M (2011) Role of the two sialic acid binding sites on the newcastle disease virus HN protein in triggering the interaction with the F protein required for the promotion of fusion. J Virol 85:12079-82
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