This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. Primary support for the subproject and the subproject's principal investigator may have been provided by other sources, including other NIH sources. The Total Cost listed for the subproject likely represents the estimated amount of Center infrastructure utilized by the subproject, not direct funding provided by the NCRR grant to the subproject or subproject staff. The model coronavirus Mouse Hepatitis Virus (MHV) is dependent upon its Spike protein for target cell binding. Once bound, Spike directs subsequent virus-cell membrane fusion thus leading to entry and by extension regulating host range. Spike protein displays the features of a Class I fusion protein, similar to the fusion proteins of Influenza. Prior research with MHV and other Class I viruses has demonstrated that mutations in and adjacent to conserved heptad repeat regions (regions vital to the fusion process) can lead to altered host range. The hypothesis is that the Spike protein has an inherent """"""""slack"""""""" in the fusion mechanism that may be exposed under certain selective environments leading to altered host range. This project has two goals. The first is to examine the biochemical properties of Spike proteins from previously isolated MHV host range mutants. The second will examine what, if any, mutations result when selective pressure is applied to the heptad repeats using a fusion inhibiting peptide, similar to the drug Fuzeon. By combining these studies, a clearer picture of how MHV can cross the species barrier should be developed and possibly extended to other Class I viruses.

Agency
National Institute of Health (NIH)
Institute
National Center for Research Resources (NCRR)
Type
Exploratory Grants (P20)
Project #
5P20RR016479-11
Application #
8360644
Study Section
Special Emphasis Panel (ZRR1-RI-4 (01))
Project Start
2011-05-01
Project End
2012-04-30
Budget Start
2011-05-01
Budget End
2012-04-30
Support Year
11
Fiscal Year
2011
Total Cost
$34,083
Indirect Cost
Name
University of South Dakota
Department
Other Basic Sciences
Type
Schools of Medicine
DUNS #
929930808
City
Vermillion
State
SD
Country
United States
Zip Code
57069
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