Abstract
Mouse mammary tumor virus (MMTV) is a virus that induces breast cancer in mice. During lactation, MMTV can transmit from mother to offspring through milk, and Peyer’s patches (PPs) in mouse intestine are the first and specific target organ. MMTV can be transported into PPs by microfold cells and then activate antigen-presenting cells (APCs) by directly binding with Toll-like receptors (TLRs) whereas infect them through mouse transferrin receptor 1 (mTfR1). After being endocytosed, MMTV is reversely transcribed and the cDNA inserts into the host genome. Superantigen (SAg) expressed by provirus is presented by APCs to cognate CD4+ T cells via MHCII molecules to induce SAg response, which leads to substantial proliferation and recruitment of related immune cells. Both APCs and T cells can be infected by MMTV and these extensively proliferated lymphocytes and recruited dendritic cells act as hotbeds for viral replication and amplification. In this case, intestinal lymphatic tissues can actually become the source of infection for the transmission of MMTV in vivo, which results in mammary gland infection by MMTV and eventually lead to the occurrence of breast cancer.
Highlights
Mouse mammary tumor virus (MMTV) is first reported by Bittner in his mouse adoptive nursing experiment which was proved to be associated with carcinogenesis between progeny and their breeders (Bittner, 1936)
The results showed that only dendritic cells (DCs) (CD11c+) were GFP positive
The delay may be ascribed to: (a) the process of MMTV ingestion, reaching the gut, and transportation via M cells in order to reach Peyer’s patches (PPs); (b) virus titers differing between methods of infection; (c) the composition of lymphocyte populations at the initial stage varying from draining lymph nodes to PPs; and (d) other interfering factors that vary among laboratories, including experimental instruments, viral activity, reagents, and operational skills
Summary
Mouse mammary tumor virus (MMTV) is first reported by Bittner in his mouse adoptive nursing experiment (he named the virus “milk factor”) which was proved to be associated with carcinogenesis between progeny and their breeders (Bittner, 1936). The subsequent in vivo inoculation experiments of viral particles isolated from mouse milk as well as the advances in experience and techniques for purifying RNA viruses confirmed that MMTV is a singlestranded type B complex retrovirus (Graff et al, 1949; Dmochowski and Grey, 1957; Duesberg and Blair, 1966). Endogenous mouse mammary tumor virus (Mtv) exists in genomes of multiple mouse strains and is passed on to offspring through germ lines. MMTV and Immune infectious viral particles but retain the ability to encode functional superantigen (SAg). The negative selection induced by SAg during thymus development deletes cognate thymocytes bearing Vb chains shapes the T cell repertoire (Salmons et al, 1986; Woodland et al, 1991; Cho et al, 1995)
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