Possible pathways of circulation of human endogenous retrovirus similar to mouse mammary tumor virus

Abstract

It is shown that polypeptides which are immunologically related to gp52 mammary tumor virus are found in T and B peripheral blood lymphocytes in all breast cancer patients, in children with B-cell lymphosarcomas, and in B lymphocytes of some healthy donors. These proteins are not found in patients with tumors of other sites. Key Words: mouse mammary tumor virus; human endogenous retrovirus; lymphocytesDuring the 1970s it was discovered that the successful transport of mouse mammary tumor virus (MMTV), which is transmitted with the milk from the digestive tract to the mammary gland, depends on the functional integrity of the immune system: thymectomy in young mice of a highly carcinogenic strain resulted in a sharp decrease of breast cancer incidence [2]. The reason recently became clear after study of the MMTV superantigens, factors that are encoded on the open reading frame of the 3' long terminal repeat of the provirus sequence [5]. Being bound with CD4 § lymphocytes which bear receptors with a specific V-B-chain, superantigens stimulate them to proliferate and initiate cell death in the same lymphocyte subpopulation during its maturation in the thymus in mice carrying only endogenous MMTV.During the study of MMTV superantigens, the use of different mouse models established that the B lymphocyte is the primary target cell for this retrovirus gene product, gp52, plays a significant role in effective superantigen presentation. In this manner, MMTV was found not only to determine the functional integrity of the immune system, but also to use the lymphocyte pathway of circulation in the mouse organism.Human endogenous retrovirus, which has been studied in detail, is akin to MMTV according to a whole complex of morphological features, antigens to structural proteins, and homology of the nucleotide sequences [3]. Expression of a protein which is an immunological analog of gp52 correlates specifically with the presence of breast cancer in human beings.However, neither the role which the endogenous MMTV-related human retrovirus plays in ~u-mor incidence nor its other biological functions have been elucidated. The pathways of its circulation in the human organism are not yet clear. We speculated that the processes in man must be similar to the lymphocytic pathway of MMTV circulation in mice, and thus sought the presence of an antigen, which would be an immunological analog of the gp52 of MMTV in lysates of peripheral blood lymphocytes in patients with tumors of different location and in healthy donors.

Evidence for a causal role by mouse mammary tumour-like virus in human breast cancer

“…33,38,39 Similarly, MMTV-infected human lymphocytes can be found in women with MMTV-positive breast cancer. 52–54 In immunocompromised mice injected with wild-type MMTV, there is no infection of peripheral lymphocytes or virus spread to the mammary glands. 50 The risk of breast cancer is reduced by 44% in immunocompromised human patients.…”

Detection of the env MMTV-homologous sequences in mammary carcinoma patient intestine lymphoid tissue

“…Antibodies specific for MMTV structural proteins were detected in 70-72% of breast cancer patients, and in 3-5% of healthy women only [2].…”

“…It is a unique oncogenic retrovirus of B type which uses lymphoid cells for circulation, it induces by insertional mutagenesis premalignant lesions and mammary carcinoma in some virusinfected mouse strains. After the ingestion of infected milk of viremic mother exogenous MMTV gets B-cells in lymphoid tissue of spleen and gut, including Peyer's patches [2]. Then MMTV integrates into the lymphoid cell genome as a provirus [3,6].…”

“…In spite of the failure of finding MMTV-related mature virus infectious for humans in breast cancer patients [2,3,10,11], there are reasons for the search for a similar viral agent in the human genome.…”