Klingel K, Kandolf R
Molecular Pathology, Institute of Pathology, University of Tübingen and Max-Planck-Institute for Biochemistry, Martinsried, Liebermeisterstr. 8, D-72076 Tübingen, Germany.
Clin Diagn Virol. 1996 May;5(2-3):157-66. doi: 10.1016/0928-0197(96)00217-6.
Enteroviruses, including coxsackieviruses of group B (CVB), are considered to be the most common agents of viral myocarditis. As demonstrated by in situ hybridization for the detection of viral RNA in endomyocardial biopsies and autopsy hearts, such infections are also detectable in patients with 'idiopathic' dilated cardiomyopathy, indicating the possibility of myocardial enterovirus persistence. Persistent enterovirus infection of the human heart is supported by the recent discovery in various murine models of chronic myocarditis, demonstrating that CVB3, typically a cytolytic virus, is capable of evading immunological surveillance in a host-dependent manner.
In order to investigate mechanisms underlying acute and persistent enterovirus infection in the myocardium, diverse tissues from CVB3 infected immunocompetent mice were processed in in situ hybridization for the detection of viral RNA. In addition, virus-host interactions were analyzed at the subcellular level in the myocardium in the course of the infection by means of an electron microscopic in situ hybridization assay.
A close spatial and temporal relationship between viral replication and inflammatory lesions was observed during the acute as well as persistent phase of myocardial infection. A multiorgan study revealed that, in addition to heart muscle cells, lymphoid cells of spleen and lymph nodes are persistently infected. The results obtained at the ultrastructural level demonstrate that loss of host cell integrity is a direct consequence of acute viral replication and confirm that chronic myocarditis may be associated with persistent heart muscle infection.
Viral replication plays a central role in the pathogenesis of acute and chronic myocarditis. Immune cells are important targets of the infection and provide a non-cardiac viral reservoir.
肠道病毒，包括B组柯萨奇病毒（CVB），被认为是病毒性心肌炎最常见的病原体。通过原位杂交检测心内膜活检组织和尸检心脏中的病毒RNA表明，在“特发性”扩张型心肌病患者中也可检测到此类感染，这表明心肌中存在肠道病毒持续感染的可能性。最近在各种慢性心肌炎小鼠模型中的发现支持了人类心脏的持续性肠道病毒感染，表明CVB3这种通常具有细胞溶解性的病毒能够以宿主依赖的方式逃避免疫监视。
为了研究心肌中急性和持续性肠道病毒感染的潜在机制，对CVB3感染的免疫活性小鼠的各种组织进行原位杂交以检测病毒RNA。此外，在感染过程中，通过电子显微镜原位杂交试验在亚细胞水平分析心肌中的病毒-宿主相互作用。
在心肌感染的急性期和持续期均观察到病毒复制与炎性病变之间存在密切的时空关系。一项多器官研究表明，除心肌细胞外，脾脏和淋巴结中的淋巴细胞也受到持续感染。超微结构水平的结果表明，宿主细胞完整性的丧失是急性病毒复制的直接后果，并证实慢性心肌炎可能与心肌持续性感染有关。
病毒复制在急性和慢性心肌炎的发病机制中起核心作用。免疫细胞是感染的重要靶点，并提供了一个非心脏的病毒储存库。
