Latent Cytomegalovirus Infection in Female Mice Increases Breast Cancer Metastasis

Abstract

Cytomegalovirus (CMV) infects 40–70% of women, but infection has been reported in >95% of breast cancer patients. We investigated the consequences of these observations by infecting mice with mCMV or a negative control medium for 4 days, 11 days or 10 weeks to establish active, intermediate or latent infections, respectively. Syngeneic 4T1 or E0771 breast cancer cells were then injected into a mammary fat pad of BALB/c or C57BL/6 mice, respectively. Infection did not affect tumor growth in these conditions, but latently infected BALB/c mice developed more lung metastases. The latent mCMV infection of MMTV-PyVT mice, which develop spontaneous breast tumors, also did not affect the number or sizes of breast tumors. However, there were more tumors that were multilobed with greater blood content, which had enhanced vasculature and decreased collagen content. Most significantly, mCMV infection also increased the number and size of lung metastases, which showed a higher cell proliferation. Viral DNA was detected in breast tumors and lung nodules although viral mRNA was not. These novel results have important clinical implications since an increased metastasis is prognostic of decreased survival. This work provides evidence that treating or preventing HCMV infections may increase the life expectancy of breast cancer patients by decreasing metastasis.