This research will be done primarily in Argentina in the Division Medicina Experimental, Academia Nacional de Medicina, in collaboration with Dr. Isabel Piazzon as an extension of NIH grant #P01 CA77760. We have been using mouse mammary tumor virus (MMTV), a retrovirus that causes mammary tumors in mice, to study virus/host interactions. MMTV is an excellent model system for the study of mucosally-acquired viruses, since it is transmitted through milk to neonatal suckling pups, infects lymphocytes in the Peyer's patches and uses these cells to spread in the animal. Our studies have focused on understanding the mechanisms which determine genetic susceptibility to MMTV infection in vivo, using different inbred, transgenic and knockout mice. This approach has led to identification of many of the steps that MMTV uses in vivo to take advantage of its host, as well an understanding of how this virus interacts with cells of the immune system. In the next funding period, we will continue to use genetic approaches to study genes that affect the interaction of MMTV with dendritic cells in the Peyer's patches. We will study the role of a family of receptors involved in innate immunity, the toll-like receptors (TLR), that we have recently shown are involved in an early step in the MMTV infection pathway, stimulation of B cells. Since dendritic cells have also been implicated in MMTV infection and are known to be one of the primary mediators of innate immune responses, understanding their role in virus infection is likely to provide insight into virus/host interactions.

Agency
National Institute of Health (NIH)
Institute
Fogarty International Center (FIC)
Type
Small Research Grants (R03)
Project #
5R03TW001103-06
Application #
6906530
Study Section
International and Cooperative Projects 1 Study Section (ICP)
Program Officer
Sina, Barbara J
Project Start
1999-09-30
Project End
2007-01-31
Budget Start
2005-08-01
Budget End
2007-01-31
Support Year
6
Fiscal Year
2005
Total Cost
$40,320
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
Courreges, Maria Cecilia; Burzyn, Dalia; Nepomnaschy, Irene et al. (2007) Critical role of dendritic cells in mouse mammary tumor virus in vivo infection. J Virol 81:3769-77
Burzyn, Dalia; Rassa, John C; Kim, David et al. (2004) Toll-like receptor 4-dependent activation of dendritic cells by a retrovirus. J Virol 78:576-84
Czarneski, Jennifer; Berguer, Paula; Bekinschtein, Pedro et al. (2002) Neonatal infection with a milk-borne virus is independent of beta7 integrin- and L-selectin-expressing lymphocytes. Eur J Immunol 32:945-56