MARKERS OF HUMAN INFECTION WITH BOVINE LEUKEMIA VIRUS

描述(申请人提供)：小鼠的乳腺癌是由一种病毒--小鼠乳腺肿瘤病毒引起的，并为人类乳腺癌的病毒病因学提供了一个模型。这种病毒通过母乳从母亲传给后代。由于人类喝的牛奶比人奶多，牛病毒可能是导致人类乳腺癌的原因之一。牛白血病病毒(BLV)是一种致癌性逆转录病毒，在全球范围内引起牛的广泛感染。白血病/淋巴瘤发生在1%受感染的牛身上，大多数保持健康，保留在牛群中，是牛肉和乳制品的来源。传染性病毒可能存在于未充分煮熟或未经巴氏灭菌的牛食品中。BLV感染牛的淋巴细胞和乳腺上皮细胞。它可以跨物种自然感染山羊和绵羊，也可以在体外感染人类细胞。越来越多的证据表明，一些人感染了BLV。在74%的人类志愿者中检测到BLV抗体。在人乳腺上皮细胞中检测到BLV蛋白和前病毒DNA。初步研究表明，与从未患过乳腺癌的女性相比，确诊为乳腺癌的女性的乳房组织中出现这种病毒的频率更高。这项研究的具体目的是：1)确定人类白细胞感染BLV的频率，并获得白细胞感染是否先于乳腺上皮细胞感染的初步线索；2)获得初步数据，以确定抗BLV抗体亚型(Ig G、Ig M、Ig A)的分布是否与BLV前病毒DNA在白细胞和/或乳腺组织中的存在有关。来自同一捐赠者的匹配的血液和乳房组织样本将从70名志愿者中获得。采用免疫印迹法(Western印迹)检测血清中抗BLV的免疫球蛋白Ig G、Ig M和Ig A抗体，用标准聚合酶链式反应和原位聚合酶链式反应检测血白细胞和乳腺组织中的BLV前病毒DNA。抗体的存在、白细胞的BLV感染、乳腺组织的BLV感染以及乳腺癌的诊断之间的相关性将被测试。这些结果应该提供初步数据，以建立一项更大规模的研究，以确定白细胞在BLV感染乳腺组织中的作用，以及白细胞中抗BLV抗体或BLV检测是否可以作为乳腺组织BLV感染的可能替代标记物，并用于预测乳腺癌的发展风险。

DESCRIPTION (provided by applicant): Breast cancer in mice is caused by a virus, mouse mammary tumor virus, and provides a model for a viral etiology of human breast cancer. This virus is transmitted from mother to offspring via milk. Since humans drink more cows' milk than human milk, a bovine virus might be a cause of human breast cancer. Bovine leukemia virus (BLV), an oncogenic retrovirus, causes widespread infection of cattle globally. Leukemia/lymphoma develops in <1% of infected cattle;, most remain healthy, are retained in the herd, and are sources of beef and dairy products. Infectious virus may be present in bovine foodstuffs not adequately cooked or pasteurized. BLV infects lymphocytes and mammary epithelial cells of cattle. It can cross species naturally to infect goats and sheep, and can infect human cells in vitro. Evidence is accumulating that some humans are infected with BLV. Antibodies to BLV were detected in 74% of human volunteers. BLV protein and proviral DNA have been detected in human breast epithelium. Preliminary studies indicate the virus is present more frequently in the breast tissue of women with a diagnosis of breast cancer vs. women who have never had breast cancer. The specific aims of the research proposed here are: 1) to determine the frequency of human leukocyte infecttion with BLV and to obtain preliminary clues about whether infection of leukocytes precedes infection of mammary epithelial cells; 2) to obtain preliminary data to determine if the profile of anti-BLV antibody isotypes (IgG, IgM, IgA) correlates with the presence of BLV proviral DNA in leukocytes and/or the breast tissue. Matched blood and breast tissue samples from the same donor will be obtained from 70 volunteers. Serum IgG, IgM, and IgA antibodies to BLV will be detected by immunoblotting (western blot), and BLV proviral DNA in blood leukocytes and breast tissue will be detected by standard PCR and in situ-PCR. The correlation of antibody presence, BLV infection of leukocytes, BLV infection of breast tissues, and a diagnosis of breast cancer will be tested. The results should provide preliminary data upon which to build a larger study to determine the role of leukocytes in breast tissue infection by BLV and whether tests for anti- BLV antibodies or BLV in leukocytes could serve as possible surrogate markers for BLV infection of breast tissue and be used to predict risk of breast cancer development.