Mouse mammary tumor virus (MMTV) is a type B retrovirus which causes mammary gland carcinomas in susceptible mice. The virus is transmitted to new born pups by nursing on infected mother's milk and results in the initial infection of B cells in the Peyer's patches. Similar to most retroviruses, MMTV infection and replication requires the target cell to be in an activated state. Currently, the mechanism of activating the initial B cell target population is not understood. The Tlr-4 protein is an integral component of the LPS signal transduction pathway which results in high levels of lymphocyte activation. We have preliminary evidence that the MMTV Env protein binds to the Tlr-4 protein. C3H/HeJ mice which are deficient in LPS induced signaling exhibit reduced MMTV virulence and reduced endogenous MMTV gene expression in the presence of LPS. The goal of this work is to understand the molecular interaction between mouse mammary tumor virus (MMTV) Env and Tlr-4 and to determine the role of Tlr-4 mediated cellular activation on the early stages of MMTV pathogenesis in B cells.

Agency
National Institute of Health (NIH)
Institute
National Cancer Institute (NCI)
Type
Postdoctoral Individual National Research Service Award (F32)
Project #
1F32CA090037-01
Application #
6294828
Study Section
Virology Study Section (VR)
Program Officer
Lohrey, Nancy
Project Start
2001-02-16
Project End
Budget Start
2001-02-16
Budget End
2002-02-15
Support Year
1
Fiscal Year
2001
Total Cost
$34,832
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
Rassa, John C; Ross, Susan R (2003) Viruses and Toll-like receptors. Microbes Infect 5:961-8
Zhang, Yuanming; Rassa, John C; deObaldia, Maria Elena et al. (2003) Identification of the receptor binding domain of the mouse mammary tumor virus envelope protein. J Virol 77:10468-78
Czarneski, Jennifer; Rassa, John C; Ross, Susan R (2003) Mouse mammary tumor virus and the immune system. Immunol Res 27:469-80