Human T-cell leukemia viruses type 1 (HTLV-1) is notorious for being difficult to study in cell culture, which has prohibited a rigorous analysis of how these viruses replicate in cells, including the steps involved in retrovirus assembly. The details for how retrovirus particle assembly occurs are poorly understood even for other more tractable retroviral systems. This proposal seeks funding to investigate two questions related to Gag trafficking in living cells using an exciting new biophysical approach. We will apply the novel single-molecule technology of fluorescence fluctuation spectroscopy (FFS) in living cells to investigate 1) HTLV-1 Gag oligomerization of wt Gag and mutants that have defects in binding proteins involved in virus budding as well as Gag mutants that have RNA packaging defects, and 2) Gag mobility and binding affinity to membrane. The results from these proposed studies should provide further insight into fundamental aspects of HTLV-1 and retrovirus particle assembly.

Public Health Relevance

Fundamental studies of HTLV-1 assembly will lead to detailed information about these processes that will be useful for a better understanding of how these viruses replicate in cells. ? ? ?

Agency
National Institute of Health (NIH)
Institute
National Institute of Allergy and Infectious Diseases (NIAID)
Type
Exploratory/Developmental Grants (R21)
Project #
1R21AI081673-01A2
Application #
7533069
Study Section
Special Emphasis Panel (ZRG1-IDM-P (91))
Program Officer
Park, Eun-Chung
Project Start
2008-06-20
Project End
2010-05-31
Budget Start
2008-06-20
Budget End
2009-05-31
Support Year
1
Fiscal Year
2008
Total Cost
$188,750
Indirect Cost
Name
University of Minnesota Twin Cities
Department
Dentistry
Type
Schools of Dentistry
DUNS #
555917996
City
Minneapolis
State
MN
Country
United States
Zip Code
55455
Fogarty, Keir H; Zhang, Wei; Grigsby, Iwen F et al. (2011) New insights into HTLV-1 particle structure, assembly, and Gag-Gag interactions in living cells. Viruses 3:770-93
Fogarty, Keir H; Chen, Yan; Grigsby, Iwen F et al. (2011) Characterization of cytoplasmic Gag-gag interactions by dual-color z-scan fluorescence fluctuation spectroscopy. Biophys J 100:1587-95
Grigsby, Iwen F; Zhang, Wei; Johnson, Jolene L et al. (2010) Biophysical analysis of HTLV-1 particles reveals novel insights into particle morphology and Gag stochiometry. Retrovirology 7:75