ROLE OF TLR 4 IN MMTV INFECTION OF B LYMPHOCYTES

University Of Pennsylvania, Philadelphia PA

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Abstract

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.