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: 7214617
• 负责人: Gertrude Case Buehring
• 金额: $ 7.38万
• 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 2009-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7214617
• 关键词: Antibodies; Antibody Formation; Blood; Blood Tests; Bos taurus; Bovine Leukemia Virus; Bovine leukemia; Breast; Breast Cancer Epidemiology; Breast Cancer Risk Factor; Cancer Control; Cancer Etiology; Cattle; Cells; DNA; Dairy Products; Data; Development; Disease; Epidemic; Epidemiologic Studies; Epithelial Cells; Epithelium; Etiology; Exposure to; Female; Frequencies; Genetic; Genus Capra; Goat; Hormones; Human; Human Milk; Human Volunteers; Immunoglobulin A; Immunoglobulin G; Immunoglobulin M; In Situ; In Vitro; Incidence; Individual; Infection; Lead; Leukocytes; Lymphocyte; Malignant Neoplasms; Mammary Gland Parenchyma; Mammary gland; Measurable; Milk; Modeling; Mothers; Mus; Natural History; Neoplasms; Oncogenic; Pathway interactions; Polymerase Chain Reaction; Population Control; Prevention; Procedures; Process; Recording of previous events; Reproductive History; Research; Retroviridae; Risk; Risk Factors; Role; Sampling; Serum; Sheep; Source; Standards of Weights and Measures; Surrogate Markers; Testing; Tissue Sample; Viral; Viral Proteins; Virus; Virus Diseases; Western Blotting; Woman; base; beef; breast cancer diagnosis; cancer cell; cancer type; cooking; diet and cancer; drinking; exposed human population; improved; leukemia virus; leukemia/lymphoma; malignant breast neoplasm; mammary epithelium; mammary tumor virus; promoter; trafficking; volunteer

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（由申请方提供）：小鼠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模型。这种病毒通过乳汁从母亲传染给后代。由于人类喝的牛奶比人乳多，牛病毒可能是人类乳腺癌的一个原因。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。白血病/淋巴瘤在<1%的受感染牛中发展;大多数保持健康，留在牛群中，是牛肉和乳制品的来源。感染性病毒可能存在于未经充分煮熟或巴氏消毒的牛类食品中。BLV感染牛的淋巴细胞和乳腺上皮细胞。它可以自然地跨物种感染山羊和绵羊，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妇女相比，该病毒更频繁地存在于诊断为乳腺癌的妇女的乳腺组织中。本文提出的研究的具体目的是：1）确定人类白细胞感染BLV的频率，并获得关于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，伊加）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供体的匹配血液和乳腺组织样本。将通过免疫印迹法（western blot）检测血清中BLV IgG、IgM和伊加抗体，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、白细胞的BLV感染、乳腺组织的BLV感染和乳腺癌诊断的相关性。结果应提供初步数据，在此基础上建立一个更大的研究，以确定白细胞在乳腺组织感染BLV的作用，以及白细胞中的抗BLV抗体或BLV检测是否可以作为乳腺组织BLV感染的可能替代标志物，并用于预测乳腺癌发展的风险。