Sendai virus is an enveloped virus which infects cells by fusion of its envelope or membrane with that of its traget cell. This infection-by-fusion mechanism is common to other viruses, including influenza, and also serves as a paradigm for a host of biologically important types of membrane fusion not involving viruses but responsible for processes such as communication between membrane-bounded compartments of the cell, secretion, uptake of materials by the cell and other processes, such as fertilization and muscle cell differentiation. The fusion of Sendai virus with its target membrane involves, fist, binding of a viral envelope protein to a receptor protein on the target cell, followed by a perturbation and disruption of the target membrane by a fusion protein on the viral membrane so that the viral membrane becomes one with the target membrane. It is proposed to isolate lipid and protein receptors of Senai virus from Ehrlich ascites tumor cells, which are capable of supporting Sendai virus multiplication. The isolated receptors will be purified and reconstituted with membrane-forming lipids into artificial membranes, which will be tested for their ability to serve as model target membranes for Sendai virus. The ability of the receptor containing membranes to bind to, to be lysed by or to fuse with the viral membrane in a manner analogous to that of natural target membranes will be measured so that the combination of components minimally necessary to give the most active target membrane will be identified. Not only will this study result in the isolation of receptors from productively infectable cells for future study of their role in mediating the infectability, it will afford a model membrane optimized for use in future studies of the molecular mechanism of viral-target membrane fusion, as well as a strategy for the investigation of interactions between non-fusing and non-enveloped viruses and model target membranes reconstituted with their receptors from infectable cells. This innovative strategy will constitute an advance in virus technology which should facilitate and, therefore, stimulate investigation of virus adsorption and penetration, the first and often determinant step in virus infection of cells.

Agency
National Institute of Health (NIH)
Institute
National Institute of Allergy and Infectious Diseases (NIAID)
Type
Research Project (R01)
Project #
5R01AI020421-02
Application #
3130100
Study Section
Experimental Virology Study Section (EVR)
Project Start
1984-12-01
Project End
1987-11-30
Budget Start
1985-12-01
Budget End
1987-11-30
Support Year
2
Fiscal Year
1986
Total Cost
Indirect Cost
Name
Northwestern University at Chicago
Department
Type
Schools of Arts and Sciences
DUNS #
City
Evanston
State
IL
Country
United States
Zip Code
60208