Viral entry into the host cell is generally considered the initial step of infection, and as such, determining the mechanism of entry is critical for understanding the virus life cycle. In addition, the specificity of entry is one of the major determinants of viral tropism and pathogenesis. Viral entry has thus provided an attractive target for antiviral therapy, not only in terms of blocking virus attachment to the host cell, but also in terms of inhibiting envelope-mediated fusion. Also, understanding entry has proven essential for potential genetic therapy applications, in which many strategies call for targeting recombinant virus to a specific cell or tissue. The objective of this proposal is to outline a series of experiments designed to elucidate the mechanism of viral fusion, using the avian retrovirus Rous sarcoma virus (RSV) as a general model for viral entry. The specific goals are the following: 1) characterize envelope mutants which are defective for receptor-induced triggering; 2) investigate the role of pH in RSV entry: and 3) purify the components of the fusion apparatus for structure determination.

Agency
National Institute of Health (NIH)
Institute
National Institute of Allergy and Infectious Diseases (NIAID)
Type
Postdoctoral Individual National Research Service Award (F32)
Project #
5F32AI050341-02
Application #
6683392
Study Section
Experimental Virology Study Section (EVR)
Program Officer
Beisel, Christopher E
Project Start
2001-08-01
Project End
2003-07-31
Budget Start
2002-11-01
Budget End
2003-07-31
Support Year
2
Fiscal Year
2003
Total Cost
$31,526
Indirect Cost
Name
University of Pennsylvania
Department
Microbiology/Immun/Virology
Type
Schools of Medicine
DUNS #
042250712
City
Philadelphia
State
PA
Country
United States
Zip Code
19104
Amberg, Sean M; Netter, Robert C; Simmons, Graham et al. (2006) Expanded tropism and altered activation of a retroviral glycoprotein resistant to an entry inhibitor peptide. J Virol 80:353-9
Netter, Robert C; Amberg, Sean M; Balliet, John W et al. (2004) Heptad repeat 2-based peptides inhibit avian sarcoma and leukosis virus subgroup a infection and identify a fusion intermediate. J Virol 78:13430-9