Human Mammary Tumor Virus (HMTV) sequences in human milk

Abstract

BackgroundRetroviral sequences 90-95% homologous to the mouse mammary tumor virus (MMTV) were present in 38% of the breast cancers studied from American women and were not detectable in non-tumor breast tissue from the same patient. The entire proviral structure was described and viral particles were isolated from primary cultures of human breast cancer. This virus was designated as human mammary tumor virus (HMTV). Hormone response elements present in the HMTV Long-Terminal-Repeat (LTR) suggest a mechanism for association of HMTV with hormonally responding tissues. In fact, the incidence of HMTV sequences is higher in gestational breast cancers, which are associated with hormonal changes. Milk epithelial cells are also under hormonal regulation and therefore are excellent specimens for HMTV sequence detection.MethodsThe HMTV sequence was studied in milk samples from lactating women recruited with increased risk of breast cancer because they had undergone breast biopsies (Biopsy-Group) and lactating women without breast biopsies (Reference-Group).ResultsHMTV-env sequences were detected by PCR in milk of 7.61% of 92 women of the Reference-Group and in 20.55% of 73 women of the Biopsy-Group (p: 0.015). The sequences were 94-98% homologous to MMTV. HMTV-env and HMTV-env/LTR junction sequences were detected in high-speed pellet RNA, implying the presence of HMTV viral particles. PCR assays to detect the murine mitochondrial cytochrome oxidase gene and intracisternal-A-type particle sequences were performed to rule out mouse mitochondrial or genomic DNA contamination. Eight women of the 73 Biopsy-Group participants had breast cancer and the milk of only one of these eight women had HMTV-env sequences. In the remaining 65 women of the Biopsy-Group, under enough clinical suspicion to lead to biopsy, HMTV was detected in 14, nearly three times the number of milks as compared to the Reference-Group (21.54% versus 7.61%; p: 0.016).ConclusionThe significance of HMTV in milk from the Reference-Group, the greater frequency in the milk of women who had undergone a breast biopsy and its possible infectivity for infants are important questions under study. The similarity of HMTV to MMTV is striking and suggests one possible avenue for viral transmission in humans.

Mouse mammary tumor-like virus (MMTV) is present in human breast tissue before development of virally associated breast cancer

“…These findings correlate with different burdens of MMTV-like infection in human breast cancers, 0-20% in Asia vs. 27-60%, in the seven countries which are associated with different prevalence of MMTV in the indigenous mouse species [18, 19]. (ix) MMTV–like sequences have been identified in milk from healthy lactating women and three fold positivity in milk from women at high risk for breast cancer [20, 21], (x) MMTV-like sequences have been identified in the saliva of 27% of healthy children, 11% of healthy adults and 57% of adults with breast cancer, which is suggestive of a human to human viral transmission [22] and (xi) MMTV-like viral sequences have been identified in breast cancers which developed in a father, mother and daughter of the same family which is suggestive of an infectious condition [23]. Overall this evidence is consistent with MMTV having similar influences in both human breast cancer and mouse mammary tumors.…”

Polypyrimidine tract‐binding protein binds to the 5′ untranslated region of the mouse mammary tumor virus mRNA and stimulates cap‐independent translation initiation

“…Translation initiation of the genomic RNA of MMTV, a virus linked to mammary tumors in mouse and breast cancer in humans , can occur via an IRES‐dependent mechanism ( and Fig. ).…”

“…The Mouse Mammary Tumor Virus is a beta‐retrovirus that exists in both exogenous (MMTV) and endogenous ( Mtv ) forms (reviewed in ). MMTV is the etiological agent of mammary cancer in mice and might also be involved in breast cancers in humans . Little is known about the basic virus–host interactions leading to MMTV protein expression.…”

No significant viral transcription detected in whole breast cancer transcriptomes

“…In contrast, studies were published that failed to detect viral sequences in breast cancer [ 10 , 11 ]. Apart from the above viruses, the mouse mammary tumor virus (MMTV) has also been in the center of attention, due to its link with mammary cancer in mice, with a recent study detecting MMTV sequences in the milk of women who had undergone breast biopsies [ 12 ]. The review of Salmons et al [ 13 ] points out, as mentioned above for the other viruses, the controversy in the results between studies for the presence or not of MMTV in breast cancer and the fact that viral sequences are difficult to detect in tumors.…”