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人类免疫缺陷病毒与获得性免疫缺陷综合征:最新进展

Human immunodeficiency virus and acquired immunodeficiency syndrome: an update.

作者信息

Schnittman S M, Fauci A S

机构信息

Division of AIDS, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Maryland.

出版信息

Adv Intern Med. 1994;39:305-55.

PMID:8140958
Abstract

Research progress in the understanding of HIV and its effects on the human immune system continues at a rapid pace. Such research is yielding new ideas for chemotherapeutic agents, immunologic stimulators and modifiers, and potential vaccines. Clinical trials to test these approaches are under way. Despite the accomplishments, the epidemic progresses unchecked, resulting in continued suffering and death and enormous demands on the health care system of many nations. Clinicians have had to deal with new and difficult opportunistic infections. Yet advances in the treatment and prevention of these illnesses have benefited many AIDS victims. In the United States, the AIDS epidemic is now concentrating in the inner cities, involving injection drug users, minorities, heterosexuals, women and their offspring. In the developing world, AIDS continues to be predominantly a heterosexually transmitted disease, where more than one third of prostitutes in central African cities are infected. The major burden of the AIDS epidemic in the remainder of this and the next century will be in India and Southeast Asia, again predominantly via heterosexual spread. A great deal is now understood concerning the life cycle of HIV. More light has been shed on the interaction of HIV and CD4+ T cells, the cellular and viral factors involved in viral expression vs. latency, the function of the viral regulatory and structural proteins and the role of cytokines in regulation of HIV expression. Our understanding of the precise mechanisms whereby HIV causes a loss of CD4+ T cells remains incomplete. The direct infection and cell killing of CD4+ T cells is important and is supported by recent evidence demonstrating a high viral burden in these cells in the lymphoid tissue of patients. Over the last 1 to 2 years, there has been new evidence for indirect mechanisms of CD4+ T-cell depletion and/or dysfunction including: autoimmune reactions, perturbations of specific V beta T-cell receptor populations, infection of T-cell precursors in bone marrow and thymus, immunosuppression and dysregulation by viral proteins, possible super-antigen effects, and antigen-induced apoptosis or programmed cell death. New information has come forth in our understanding of B-cell abnormalities in HIV pathogenesis, including the putative role of IL-6 in B-cell activation and the identification of EBV in B-cell lymphomas in the CNS of patients with AIDS. It is expected that these and future discoveries concerning immunopathogenesis of HIV infection will help steer the therapeutic effort. Major strides continue to be made in the therapeutic arena for HIV infection and its complications.(ABSTRACT TRUNCATED AT 400 WORDS)

摘要

对人类免疫缺陷病毒(HIV)及其对人体免疫系统影响的认识仍在迅速取得研究进展。此类研究正在为化疗药物、免疫刺激剂和调节剂以及潜在疫苗带来新的思路。检验这些方法的临床试验正在进行。尽管取得了这些成果,但该流行病仍在 unchecked 地蔓延,导致痛苦和死亡持续存在,并给许多国家的医疗保健系统带来巨大压力。临床医生不得不应对新出现的、棘手的机会性感染。然而,这些疾病在治疗和预防方面的进展使许多艾滋病患者受益。在美国,艾滋病疫情目前集中在市中心,涉及注射吸毒者、少数族裔、异性恋者、妇女及其后代。在发展中世界,艾滋病仍然主要是一种通过异性传播的疾病,在中非城市,超过三分之一的妓女被感染。在本世纪余下时间和下个世纪,艾滋病疫情的主要负担将落在印度和东南亚,同样主要通过异性传播。目前对HIV的生命周期已有很多了解。关于HIV与CD4 + T细胞的相互作用、病毒表达与潜伏所涉及的细胞和病毒因素、病毒调节蛋白和结构蛋白的功能以及细胞因子在HIV表达调节中的作用,人们也有了更多的认识。我们对HIV导致CD4 + T细胞丧失的确切机制的理解仍不完整。CD4 + T细胞的直接感染和细胞杀伤很重要,最近的证据表明患者淋巴组织中这些细胞的病毒载量很高,这也支持了这一点。在过去的1至2年里,有新的证据表明CD4 + T细胞耗竭和/或功能障碍的间接机制包括:自身免疫反应、特定VβT细胞受体群体的紊乱、骨髓和胸腺中T细胞前体的感染、病毒蛋白引起的免疫抑制和失调、可能的超抗原效应以及抗原诱导的凋亡或程序性细胞死亡。我们对HIV发病机制中B细胞异常的理解也有了新的信息,包括白细胞介素 - 6在B细胞激活中的假定作用以及在艾滋病患者中枢神经系统B细胞淋巴瘤中发现EB病毒。预计这些以及未来关于HIV感染免疫发病机制方面的发现将有助于指导治疗工作。在HIV感染及其并发症的治疗领域继续取得重大进展。(摘要截选至400字) (注:原文中“unchecked”未翻译,因为不清楚其确切含义,可能是“不受控制的”之类的意思,需结合更多背景信息准确翻译。这里保留英文供进一步确认。)

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