IMMUNE REACTIVITY AND ONCOGENIC VIRUS INFECTIONS

免疫反应性和致癌病毒感染

• 批准号: 3163647
• 负责人: Martin S. Hirsch
• 金额: $ 14.05万
• 依托单位: MASSACHUSETTS GENERAL HOSPITAL
• 依托单位国家: 美国
• 财政年份: 1979
• 资助国家: 美国
• 起止时间: 1979-06-01 至 1989-05-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/3163647
• 关键词: Alphaherpesvirinae; B lymphocyte; Behcet's syndrome; Betaherpesvirinae; Retroviridae; T lymphocyte; autoimmune disorder; communicable disease diagnosis; cryopreservation; human tissue; immunofluorescence technique; immunopathology diagnosis; immunosuppression; interferons; kidney transplantation; latent virus infection; leukemia; leukocyte activation /transformation; leukocyte antigen typing; microorganism immunology; monoclonal antibody; mononucleosis; neoplasm /cancer genetics; neoplasm /cancer immunodiagnosis; neutrophil; oncogenic virus; pregnancy immunology; pregnancy infection; rapid diagnosis; systemic lupus erythematosus; tissue /cell culture; viral carcinogenesis; virus infection mechanism; virus replication

Virus-leukocyte interactions are critical to the outcome of infections with potentially oncogenic viruses. Leukocytes limit the replication of both viruses and cells transformed by viruses. However, viruses may also replicate in leukocytes and alter their function, inhibiting an effective response. This proposal will study the interactions of potentially oncogenic human herpesviruses with human leukocytes. Cytomegalovirus is a major cause of human disease, as a teratogen, opportunistic pathogen following blood transfusions or immunosuppression, and as a possible oncogen. We have demonstrated that CMV has a potent immunosuppressive effect onleukocyte function. The mechanisms of this CMV-induced hyporesponsiveness will be explored. Functional evaluation of specific leukocyte subsets and their interactions will be undertaken in vivo and in vitro. Attempts will be made to correct or reconstruct CMV-induced defective leukocyte responses. CMV-leukocyte associations will also be exploited to help develop rapid diagnostic assays for CMV artigens in infected granulocytes. Herpes simplex virus may also have complex interactions with human leukocytes. We have established a model of herpes simplex virus persistent infection of human T lymphoblasts. This persistent infection can either be productive or non-productive, depending on manipulations in vitro. Addition of antiviral agents (antibody, interferon, acyclovir) or temperature elevation can result in non-productive infection. Removal of antivirals, lowering of temperature, addition of phytohemagglutinin or 5-azacytidine can induce productive infection. The mechanisms underlying these events will be explored in vitro, and attempts will be made to determine the importance of methylation in the maintenance of non-productive infections. In situ molecular hybridization techniques will be used to determine the numbers of cells that are infected during productive and non-productive infections. The same techniques will be used to investigate the recent suggestion that certain human diseases, e.g. Behcet's syndrome, are associated with lymphocytes carrying latent herpes simplex DNA. Our herpes model will also be used to explore interactions between antiviral agents and persistent infections.

病毒与白细胞的相互作用对感染艾滋病的结局至关重要 潜在致癌病毒。白细胞限制了两者的复制 病毒和由病毒转化的细胞。然而，病毒也可能 在白细胞中复制并改变其功能，抑制有效的 回应。这项提议将研究潜在的 致癌性人类疱疹病毒与人白细胞。 巨细胞病毒是人类疾病的主要原因，作为一种致畸剂， 输血或免疫抑制后的机会性病原体， 作为可能的致癌基因。我们已经证明了CMV具有强大的 对白细胞功能的免疫抑制作用。这其中的机制 我们将探讨巨细胞病毒引起的低反应性。功能评估 特定的白细胞亚群及其相互作用将在 体内和体外。将尝试更正或重建 巨细胞病毒引起的缺陷白细胞反应。巨细胞病毒-白细胞协会将 也可以用来帮助开发CMV抗原的快速诊断方法 在受感染的粒细胞中。 单纯疱疹病毒也可能与人类有复杂的相互作用 白细胞。我们已经建立了一种持续存在的单纯疱疹病毒模型 人T淋巴母细胞感染。这种持续感染可能是 生产或非生产，取决于体外操作。 添加抗病毒药物(抗体、干扰素、阿昔洛韦)或 温度升高可能导致非生产性感染。删除 抗病毒药物、降温、添加植物血凝素或 5-氮胞苷可诱导生殖性感染。潜在的机制 这些事件将在体外进行探索，并将尝试 确定甲基化在维持乳汁中的重要性 非生产性感染。原位分子杂交技术将 用于确定在此期间感染的细胞数量 生产性和非生产性感染。将使用相同的技术 为了调查最近关于某些人类疾病，例如 白塞氏综合征与携带潜伏疱疹的淋巴细胞有关 单纯DNA。我们的疱疹模型也将用于探索相互作用 在抗病毒药物和持续性感染之间。