MMTV Env encodes an ITAM responsible for transformation of mammary epithelial cells in three-dimensional culture.

Expression of immunoreceptor tyrosine-based activation motif (ITAM)-containing signaling proteins is normally restricted to hematopoietic tissues. The basal activity of ITAM-containing proteins is mediated through negative regulation by coreceptors restricted to hematopoietic tissues. We have identified an ITAM signaling domain encoded within the env gene of murine mammary tumor virus (MMTV).

Toll-like receptor 4-dependent activation of dendritic cells by a retrovirus.

Mouse mammary tumor virus (MMTV) is a milk-borne retrovirus that exploits the adaptive immune system. It has recently been shown that MMTV activates B cells via Toll-like receptor 4 (TLR4), a molecule involved in innate immune responses. Here, we show that direct virus binding to TLR4 induced maturation of bone marrow-derived dendritic cells and up-regulated expression of the MMTV entry receptor (CD71) on these cells.

Identification of the receptor binding domain of the mouse mammary tumor virus envelope protein.

Mouse mammary tumor virus (MMTV) is a betaretrovirus that infects rodent cells and uses mouse transferrin receptor 1 for cell entry. To characterize the interaction of MMTV with its receptor, we aligned the MMTV envelope surface (SU) protein with that of Friend murine leukemia virus (F-MLV) and identified a putative receptor-binding domain (RBD) that included a receptor binding sequence (RBS) of five amino acids and a heparin-binding domain (HBD). Mutation of the HBD reduced virus infectivity, and soluble heparan sulfate blocked infection of cells by wild-type pseudovirus.

Viruses and Toll-like receptors.

Recently a number of viruses, including a poxvirus, herpesvirus, retrovirus and two paramyxoviruses, have been shown to activate cells via Toll-like receptor family members. Here we postulate that although activation via Toll-like receptor molecules can lead to anti-viral innate immune responses, in some cases viruses may use these responses to ameliorate infection.

Mouse mammary tumor virus and the immune system.

Mouse mammary tumor virus (MMTV) is a nonacute transforming retrovirus that causes mammary tumors in susceptible strains of mice. Upon milk-borne transmission, B cells in the gut become infected and subsequently present a virus-encoded superantigen to cognate T cells. These T cells become activated and, in turn, stimulate neighboring lymphocytes, thereby establishing an infection-competent reservoir of lymphoid cells.

Murine retroviruses activate B cells via interaction with toll-like receptor 4.

Although most retroviruses require activated cells as their targets for infection, it is not known how this is achieved in vivo. A candidate protein for the activation of B cells by either mouse mammary tumor virus (MMTV) or murine leukemia virus is the toll-like receptor 4 (TLR4), a component of the innate immune system. MMTV caused B cell activation in C3H/HeN mice but not in C3H/HeJ or BALB/c (C.