VIRUS-CELL INTERACTIONS LEADING TO IMMUNOSUPPRESSION

病毒与细胞相互作用导致免疫抑制

• 批准号: 2070680
• 负责人: Robert S Fujinami
• 金额: $ 16.01万
• 依托单位: UNIVERSITY OF UTAH
• 依托单位国家: 美国
• 财政年份: 1994
• 资助国家: 美国
• 起止时间: 1994-03-01 至 1997-02-28
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/2070680
• 关键词: B lymphocyte; T lymphocyte; antibody formation; antigen presentation; antisense nucleic acid; athymic mouse; cell differentiation; cytokine; gene expression; host organism interaction; human tissue; immunosuppression; lymphocyte proliferation; macrophage; measles; measles virus; microorganism immunology; nucleic acid hybridization; ribozymes; tissue /cell culture; virus RNA; virus protein; virus replication

Viruses can cause injury to the host directly, in concert with the host's immune response or by modulating the immune response such that the host is more susceptible to secondary infections. Ultimately, the anti-viral immune response is responsible for the survival of the host. This interaction between the invading microbe and the immune system has been evolving over the millennia. Some virus have acquired the ability to immunosuppress the host allowing for better spread and possible persistence. One mechanism is the infection of lymphoid cells. Infection of these cell types could lead to the modulation or suppression of the antiviral immune response. Measles virus has adapted to perform these tasks. As part of this measles virus is able to immunosuppress the host by infecting lymphoid cells. The ability of the virus to infect and alter the functions of various immune cell types have been documented. For example, natural killer (NK) cell function is compromised when infected with measles virus. Similarly, infected B cells produce much less immunoglobulin when stimulated with mitogen than uninfected B cells. While the immunosuppression is substantiated, the mechanism as to how this occurs is not known. We propose to investigate the replication of measles virus in human lymphoid cells and T cell lines/clones, as well as, B cells. In addition, we will study the effects of infection on the ability of B cells and macrophages to present specific antigens to T cell lines/clones. The importance of these studies will be to determine how infection of lymphocytes by measles virus can alter functional response to antigen. Lastly, studies are proposed to define what viral gene products can modulate lymphocyte function will be performed and how this can be reversed. These studies will provide ways to inhibit virus replication and minimize infection. Thus, this investigation will contribute to our understanding of virus-cell relationships.

病毒可以直接对宿主造成伤害，与宿主的身体状况相配合。 免疫反应或通过调节免疫反应使宿主 更容易受到继发感染。最终，抗病毒 免疫反应负责宿主的生存。这 入侵微生物与免疫系统之间的相互作用 历经千年的演变。有些病毒已经获得了以下能力： 免疫抑制宿主，从而更好地传播并可能 坚持。一种机制是淋巴细胞的感染。感染 这些细胞类型可能导致调节或抑制 抗病毒免疫反应。 麻疹病毒已适应执行这些任务。作为麻疹的一部分 病毒能够通过感染淋巴细胞来抑制宿主的免疫。这 病毒感染和改变各种免疫功能的能力 细胞类型已被记录。 例如，自然杀伤（NK）细胞 感染麻疹病毒后，功能会受到损害。相似地， 受感染的 B 细胞在受到刺激时产生的免疫球蛋白要少得多 比未感染的 B 细胞有丝分裂原。虽然免疫抑制是 虽然已得到证实，但这种现象如何发生的机制尚不清楚。 我们建议研究麻疹病毒在人类中的复制 淋巴细胞和 T 细胞系/克隆，以及 B 细胞。此外， 我们将研究感染对 B 细胞能力的影响 巨噬细胞向 T 细胞系/克隆呈递特定抗原。 这 这些研究的重要性在于确定感染是如何发生的 麻疹病毒引起的淋巴细胞可以改变对抗原的功能反应。 最后，建议进行研究来定义病毒基因产物可以 将执行调节淋巴细胞功能以及如何执行 颠倒了。这些研究将提供抑制病毒复制和 最大限度地减少感染。 因此，这项调查将有助于我们 了解病毒与细胞的关系。