MARKERS OF HUMAN INFECTION WITH BOVINE LEUKEMIA VIRUS

人类感染牛白血病病毒的标志物

• 批准号: 7116602
• 负责人: Gertrude Case Buehring
• 金额: $ 7.14万
• 依托单位: UNIVERSITY OF CALIFORNIA BERKELEY
• 依托单位国家: 美国
• 财政年份: 2006
• 资助国家: 美国
• 起止时间: 2006-04-01 至 2008-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7116602
• 关键词: DNA; antibody; breast neoplasms; clinical research; human; infection; leukocytes; mammary gland; neoplasm /cancer; tissues

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.

描述（由申请人提供）：小鼠乳腺癌是由病毒、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模型。这种病毒通过乳汁从母亲传播给后代。由于人类喝的牛奶比人奶多，因此牛病毒可能是导致人类乳腺癌的原因。牛白血病病毒（BLV）是一种致癌逆转录病毒，在全球范围内引起牛的广泛感染。 <1% 的受感染牛患白血病/淋巴瘤；大多数仍保持健康，保留在牛群中，并且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。它可以自然跨物种感染山羊和绵羊，并且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。 74% 的人类志愿者体内检测到了 BLV 抗体。在人类乳腺上皮细胞中已检测到 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，被诊断患有乳腺癌的女性的乳腺组织中存在该病毒的频率更高。本研究的具体目的是：1）确定BLV感染人类白细胞的频率，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 抗体同种型（IgG、IgM、IgA）的谱是否与白细胞和/或乳腺组织中 BLV 前病毒 DNA 的存在相关。将从 70 名志愿者中获得来自同一捐献者的匹配血液和乳腺组织样本。通过免疫印迹（蛋白质印迹）检测血清中针对 BLV 的 IgG、IgM 和 IgA 抗体，并通过标准 PCR 和原位 PCR 检测血液白细胞和乳腺组织中的 BLV 前病毒 DNA。将测试抗体存在、白细胞 BLV 感染、乳腺组织 BLV 感染和乳腺癌诊断的相关性。结果应提供初步数据，据此开展更大规模的研究，以确定白细胞在 BLV 乳腺组织感染中的作用，以及白细胞中抗 BLV 抗体或 BLV 的检测是否可以作为乳腺组织 BLV 感染的可能替代标志物，并用于预测乳腺癌发生的风险。