The Filoviruses Ebola and Marburg are highly pathogenic and contagious viruses making them a potential bioweapon. The lethal nature of these agents has made them difficult to study because of the requirement for biosafety level 4 containment. However, individual components of these virions can be safely studied in isolation. Envelope function can be studied in the context of pseudotypes and virus-like particles can be generated by the expression of the matrix protein. Recently, we have developed methods that allow the visualization of HIV using fluorescent deconvolution microscopy. With these tools it is possible to directly observe virus binding and entry into target cells in real time. These direct observations of particle behavior have provided important new insights into how HIV interacts with target cells. The goal of this application is to adapt these methods to study filovirus entry. Envelope function will be studied in two contexts. First, fluorescently labeled HIV will be pseudotyped with filovirus envelope. These studies should provide new insights into the entry pathway for Ebola and Marburg. Secondly, we will develop a system using a green fluorescent protein (GFP) tagged matrix protein (VP40) to visualize VLPs that contain the filovirus envelope. The VLP system will require extensive development and validation but offers the opportunity to study the interaction of replication defective filovirus particles with target cells. Direct visualization of these viruses will provide important new insights into how these agents bind to and enter target cells. ? ?

Agency
National Institute of Health (NIH)
Institute
National Institute of Allergy and Infectious Diseases (NIAID)
Type
Exploratory/Developmental Grants (R21)
Project #
5R21AI054495-02
Application #
6726136
Study Section
Virology Study Section (VR)
Program Officer
Repik, Patricia M
Project Start
2003-04-01
Project End
2005-03-31
Budget Start
2004-04-01
Budget End
2005-03-31
Support Year
2
Fiscal Year
2004
Total Cost
$272,773
Indirect Cost
Name
University of Illinois at Chicago
Department
Microbiology/Immun/Virology
Type
Schools of Medicine
DUNS #
098987217
City
Chicago
State
IL
Country
United States
Zip Code
60612
Bhattacharyya, Suchita; Hope, Thomas J (2013) Cellular factors implicated in filovirus entry. Adv Virol 2013:487585
Bhattacharyya, Suchita; Hope, Thomas J (2011) Full-length Ebola glycoprotein accumulates in the endoplasmic reticulum. Virol J 8:11
Bhattacharyya, Suchita; Warfield, Kelly L; Ruthel, Gordon et al. (2010) Ebola virus uses clathrin-mediated endocytosis as an entry pathway. Virology 401:18-28