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呼吸道合胞病毒对 T 细胞免疫的损害:针对毒力机制的治疗和预防。

Impairment of T cell immunity by the respiratory syncytial virus: targeting virulence mechanisms for therapy and prophylaxis.

机构信息

Departamento de Genética Molecular y Microbiología, Facultad de Ciencias Biológicas, Pontificia Universidad Católica de Chile, Alameda 340, Santiago 8331010, Chile.

出版信息

Curr Med Chem. 2009;16(34):4609-25. doi: 10.2174/092986709789760724.

Abstract

Worldwide, Respiratory Syncytial Virus (RSV) causes severe bronchiolitis and pneumonia in children, the elderly and immuno-compromised individuals. Moreover, RSV is the mayor cause of infant hospitalization due to lower respiratory infection, regardless socioeconomic status. Accumulating data support the notion that immune responses elicited against naturally acquired RSV infections are non-lasting and inappropriate for efficient virus clearance. Although there is consensus over the capacity of RSV to impair the development of an effective and protective adaptive immune response, very little is known about specific viral determinants involved in these processes as well as the molecular mechanisms developed by this virus to inhibit T cell function. Recent studies have provided evidence supporting an important role for dendritic cells in RSV-induced suppression of immunity. Although recognized for over 50 years as an important respiratory pathogen and healthcare problem, to date there are no available vaccines against this virus, which highlights the complexity of RSV-induced immunopathology. The development of new prophylactic and therapeutic tools against RSV requires the unveiling of molecular mechanisms and virulence factors responsible for the pathogenesis caused by this virus. In this review, we discuss recent findings describing virulence mechanisms evolved by RSV to negatively modulate the adaptive immune response in the host. Furthermore, novel strategies aimed to induce efficient T cell immunity against RSV are reviewed.

摘要

在全球范围内,呼吸道合胞病毒(RSV)可导致儿童、老年人和免疫功能低下者发生严重的细支气管炎和肺炎。此外,无论社会经济地位如何,RSV 是导致婴儿因下呼吸道感染而住院的主要原因。越来越多的数据支持这样一种观点,即针对自然获得性 RSV 感染产生的免疫反应是非持久的,不适合有效清除病毒。尽管人们普遍认为 RSV 能够损害有效的适应性免疫反应的发展,但对于参与这些过程的特定病毒决定因素以及该病毒为抑制 T 细胞功能而开发的分子机制知之甚少。最近的研究提供了证据,支持树突状细胞在 RSV 诱导的免疫抑制中的重要作用。尽管 RSV 作为一种重要的呼吸道病原体和医疗保健问题已被认识超过 50 年,但迄今为止还没有针对该病毒的可用疫苗,这突出了 RSV 诱导的免疫病理学的复杂性。开发针对 RSV 的新的预防性和治疗性工具需要揭示导致该病毒引起的发病机制的分子机制和毒力因子。在这篇综述中,我们讨论了最近的研究结果,这些结果描述了 RSV 进化出的毒力机制,这些机制可负调控宿主中的适应性免疫反应。此外,还回顾了诱导针对 RSV 的有效 T 细胞免疫的新策略。

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