The mouse mammary tumour virus - like virus in hormonally influenced human tissues

The identification of Mouse Mammary Tumour Virus (MMTV) as the causal factor for breast cancer in mice, initiated investigation into a viral cause for human breast cancer. MMTV-like virus has been detected in human breast cancers, lymphomas and primary biliary cirrhosis (PBC), suggesting the virus is not restricted to human breast cancers. We hypothesized that the virus is detected in human tissues influenced by steroid hormones. We detected a region of the envelope (env) gene of MMTV-like virus in 53/210 (25%) of liver disease, 4/21 (19%) of hepatocellular carcinoma (HCC), 14/89 (16%) of ovarian cancer, 53/147 (36%) of prostate cancer, 5/50 (10%) of endometrial cancer and 13/141 (9%) of skin cancer samples but not in lung cancers (0/51). Viral env DNA was also detected in 4/81 (5%) of placentae and 5/90 (6%) of breast milk cells from healthy women whilst viral env RNA was detected in 2/90 (2%) of breast milk supernatants and (0/81) placentae. Immunohistochemistry staining for the presence of estrogen receptor alpha (ER-α) and progesterone receptor (PgR) demonstrated a significant association between ER-α/PgR and MMTV-like virus in human ovarian, prostate, endometrial and skin cancers though no significant association was observed between ER-α/PgR and the virus in liver tissues. We were also unable to demonstrate a significant association between accumulation of p53 tumour suppressor protein and MMTV-like virus in liver disease and HCC. Despite the demonstration of viral env integration in genomic DNA from human placentae using Southern Blots, other regions of the virus were not detected following PCR attempts with published primer sets. This study adds to the current knowledge of distribution of MMTV-like virus in humans. The detection of the virus in hormonally influenced human tissues (positive for ER-α or PgR) indicates an association between MMTV-like virus and steroid hormones in some human tissues. The detection of the virus in placentae and breast milk also suggests potential routes of transmission of the virus in humans. Although the exact role of the virus in these tissues is not known, the presence of the virus together with other genetic alterations and/or the influence of steroid hormones could be involved in the transformation of various human tissues (i.e.pathogenesis)

Mouse mammary tumor virus-like sequences in human breast cancer

Mouse mammary tumor virus (MMTV) sequences have been reported to be present in some human breast cancers, but it is unclear whether they have any causal role. In mice, MMTV promotes tumor formation indirectly by insertional mutagenesis of Wnt oncogenes that lead to their activation. In this study, we investigated the status of Wnt-1 in human breast cancers harboring MMTV-like sequences encoding viral envelope (env) genes. We confirmed the detection of env sequences in the nucleus of human breast cancer specimens that are similar in appearance to mouse mammary tumors expressing MMTV env sequences. MMTV env sequences in human breast cancers were also nearly indistinguishable from env sequences in mouse MMTV isolates. Further, Wnt-1 expression was higher in specimens of env-positive ductal carcinoma in situ and invasive ductal carcinoma, relative to env-negative specimens. Our findings extend the evidence that MMTV sequences found in naturally occurring mouse mammary tumors can be found in some human breast cancers, prompting further evaluation of causal roles in these settings.10 page(s

Stability of Hepatitis C Virus, HIV, and Hepatitis B Virus Nucleic Acids in Plasma Samples after Long-Term Storage at −20oC and −70oC ▿

The storage of biological samples may affect detection of viral nucleic acid, yet the stability of viral nucleic acid at standard laboratory storage temperatures (−70°C and −20°C) has not been comprehensively assessed. Deterioration of viral RNA and DNA during storage may affect the detection of viruses, thus leading to an increased likelihood of false-negative results on diagnostic testing. The viral loads of 99 hepatitis C virus (HCV), 41 HIV, and 101 hepatitis B virus (HBV) patient samples were measured before and after storage at −20°C and −70°C for up to 9.1 years using Versant branched DNA assays, Cobas Monitor assays, and/or AmpliPrep/AmpliScreen assays. Clinical samples stored at −20°C for up to 1.2 years and at −70°C for up to 9 years showed a statistically significant difference from baseline with respect to HCV RNA titer, although this difference was not greater than 0.5 log10 unit. The concentration of HIV RNA in clinical samples stored at −20°C for 2.3 years and at −70°C for up to 9.1 years did not differ significantly from the baseline viral load. HBV DNA-positive clinical samples stored at −20°C for up to 5 years and at −70°C for up to 4 years differed significantly in viral load. In all studies, however, the loss of viral load of HCV, HIV, or HBV in clinical samples tested after storage at −20°C and −70°C for up to 9 years ranged from 0.01 to 0.35 log10 IU/ml and did not exceed 0.5 log10, which is the estimated intra-assay variation for molecular tests. Hence, the loss was considered of minimal clinical impact and adequate for the detection of HCV, HIV-1, and HBV nucleic acids using nucleic acid assays for the assessment of the infectious risk of cell, blood, and tissue donors