The Viral Origin of Human Breast Cancer: From the Mouse Mammary Tumor Virus (MMTV) to the Human Betaretrovirus (HBRV)

Abstract

A Human Betaretrovirus (HBRV) has been identified in humans, dating as far back as about 4500 years ago, with a high probability of it being acquired by our species around 10,000 years ago, following a species jump from mice to humans. HBRV is the human homolog of the MMTV (mouse mammary tumor virus), which is the etiological agent of murine mammary tumors. The hypothesis of a HMTV (human mammary tumor virus) was proposed about 50 years ago, and has acquired a solid scientific basis during the last 30 years, with the demonstration of a robust link with breast cancer and with PBC, primary biliary cholangitis. This article summarizes most of what is known about MMTV/HMTV/HBRV since the discovery of MMTV at the beginning of last century, to make evident both the quantity and the quality of the research supporting the existence of HBRV and its pathogenic role. Here, it is sufficient to mention that scientific evidence includes that viral sequences have been identified in breast-cancer samples in a worldwide distribution, that the complete proviral genome has been cloned from breast cancer and patients with PBC, and that saliva contains HBRV, as a possible route of inter-human infection. Controversies that have arisen concerning results obtained from human tissues, many of them outdated by new scientific evidence, are critically discussed and confuted.

Predictive modeling for breast cancer classification in the context of Bangladeshi patients by use of machine learning approach with explainable AI

“…The SoftMax layer of the neural network was switched out for a layer of Support Vector Machine. With an accuracy of 99.04%, GRU Support Vector Machine performed best in that study 20 . Cross-validation was used by Karabatak et al 21 to improve the accuracy of a model trained with association rules and a neural network to 95.6%.…”

Global Down-regulation of Gene Expression Induced by Mouse Mammary Tumor Virus (MMTV) in Normal Mammary Epithelial Cells

“…MMTV is a well-known tumor-inducing pathogen in mice. In recent years, it has emerged as a potential pathogen in humans as well [ 35 , 36 , 37 , 38 , 39 ]. Therefore, it is important to study virus–host interactions to understand the host defense mechanisms at play and how the virus may evade such processes at the molecular level and spread within the host to cause disease.…”

“…It is interesting to note that unlike other cancer-causing viruses, MMTV does not encode any oncogene, and MMTV-associated carcinogenesis depends upon the host immune response, viral strain, viral proteins, especially Env and Sag, host–immune response modification by the virus, or the presence of endogenous Mtvs [ 32 , 33 , 34 , 35 ]. Furthermore, MMTV may also be jumping the species barrier into humans since MMTV-like antigens, virus particles, and sequences have been detected in the human milk, both in normal and breast cancer samples [ 36 , 37 , 38 , 39 , 40 ]. Moreover, a cloned MMTV provirus has been shown to effectively infect mouse as well as human cells [ 41 , 42 ].…”

The Host miR-17-92 Cluster Negatively Regulates Mouse Mammary Tumor Virus (MMTV) Replication via miR-92a by Targeting the Viral Genome

“…The mouse mammary tumor virus (MMTV) is a betaretrovirus shown to cause breast cancer and lymphoma/leukemia in mice. Since its discovery in the 1930s, its antigens and sequences have been observed in human breast cancer as well, leading to the controversial possibility of a human mammary tumor virus (HMTV) (Amarante et al, 2019; Bevilacqua, 2022; Parisi et al, 2022). MMTV is a classic example of a slow-transforming retrovirus that causes cancer via insertional mutagenesis in mice over a period of 6-9 months where it integrates upstream of host genes involved in regulating growth and proliferation, such as Wnt1, Fgf3, Rspo, and Notch4 (Dudley et al, 2016; Ross, 2010).…”