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Research Paper|Volume 12, Issue 16|pp 15978—15994

A human MMTV-like betaretrovirus linked to breast cancer has been present in humans at least since the copper age

Francesca Lessi5, Nicole Grandi3, Chiara Maria Mazzanti5, Prospero Civita1, Cristian Scatena1, Paolo Aretini5, Pasquale Bandiera4, Antonio Fornaciari2, Valentina Giuffra2, Gino Fornaciari2, Antonio Giuseppe Naccarato1, Enzo Tramontano3, Generoso Bevilacqua1,6
  • 1Division of Pathology, Department of Translational Research and New Technologies in Medicine, University of Pisa, Pisa, Italy
  • 2Division of Paleopathology, Department of Translational Research and New Technologies in Medicine, University of Pisa, Pisa, Italy
  • 3Division of Molecular Virology, Department of Life and Environmental Sciences, University of Cagliari, Cagliari, Italy
  • 4Center for Anthropological, Paleopathological and Historical Studies of The Sardinian and Mediterranean Populations, Department of Biomedical Sciences, University of Sassari, Sassari, Italy
  • 5Fondazione Pisana per la Scienza, Pisa, Italy
  • 6Department of Laboratory Medicine, “San Rossore” Hospital, Pisa, Italy
* Equal contribution
Received: March 24, 2020Accepted: June 22, 2020Published: July 31, 2020
https://doi.org/10.18632/aging.103780

Copyright © 2020 Lessi et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY 3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

Abstract

The betaretrovirus Mouse Mammary Tumor Virus (MMTV) is the well characterized etiological agent of mammary tumors in mice. In contrast, the etiology of sporadic human breast cancer (BC) is unknown, but accumulating data indicate a possible viral origin also for these malignancies. The presence of MMTVenv-like sequences (MMTVels) in the human salivary glands and saliva supports the latter as possible route of inter-human dissemination. In the absence of the demonstration of a mouse-man transmission of MMTV, we considered the possibility that a cross-species transmission could have occurred in ancient times. Therefore, we investigated MMTVels in the ancient dental calculus, which originates from saliva and is an excellent material for paleovirology. The calculus was collected from 36 ancient human skulls, excluding any possible mouse contamination. MMTV-like sequences were identified in the calculus of 6 individuals dated from the Copper Age to the 17th century. The MMTV-like sequences were compared with known human endogenous betaretroviruses and with animal exogenous betaretroviruses, confirming their exogenous origin and relation to MMTV. These data reveal that a human exogenous betaretrovirus similar to MMTV has existed at least since 4,500 years ago and indirectly support the hypothesis that it could play a role in human breast cancer.