Mouse Mammary Tumor Virus (MMTV) and MMTV-like Viruses: An In-depth Look at a Controversial Issue

Since its discovery as a milk factor, mouse mammary tumor virus (MMTV) has been shown to cause mammary carcinoma and lymphoma in mice. MMTV infection depends upon a viral superantigen (sag)-induced immune response and exploits the immune system to establish infection in mammary epithelial cells when they actively divide. Simultaneously, it avoids immune responses, causing tumors through insertional mutagenesis and clonal expansion. Early studies identified antigens and sequences belonging to a virus homologous to MMTV in human samples. Several pieces of evidence fulfill a criterion for a possible causal role for the MMTV-like virus in human breast cancer (BC), though the controversy about whether this virus was linked to BC has raged for over 40 years in the literature. In this review, the most important issues related to MMTV, from its discovery to the present days, are retraced to fully explore such a controversial issue. Furthermore, the hypothesis of an MMTV-like virus raised the question of a potential zoonotic mouse–man transmission. Several studies investigate the role of an MMTV-like virus in companion animals, suggesting their possible role as mediators. Finally, the possibility of an MMTV-like virus as a cause of human BC opens a new era for prevention and therapy.