Vannella Kevin M, Moore Bethany B
Department of Internal Medicine, University of Michigan Medical School, Ann Arbor, MI 48109, USA.
Fibrogenesis Tissue Repair. 2008 Oct 13;1(1):2. doi: 10.1186/1755-1536-1-2.
Idiopathic pulmonary fibrosis (IPF) remains exactly that. The disease originates from an unknown cause, and little is known about the mechanisms of pathogenesis. While the disease is likely multi-factorial, evidence is accumulating to implicate viruses as co-factors (either as initiating or exacerbating agents) of fibrotic lung disease. This review summarizes the available clinical and experimental observations that form the basis for the hypothesis that viral infections may augment fibrotic responses. We review the data suggesting a link between hepatitis C virus, adenovirus, human cytomegalovirus and, in particular, the Epstein-Barr gammaherpesvirus, in IPF. In addition, we highlight the recent associations made between gammaherpesvirus infection and lung fibrosis in horses and discuss the various murine models that have been used to investigate the contribution of gammaherpesviruses to fibrotic progression. We review the work demonstrating that gammaherpesvirus infection of Th2-biased mice leads to multi-organ fibrosis and highlight studies showing that gammaherpesviral infections of mice either pre- or post-fibrotic challenge can augment the development of fibrosis. Finally, we discuss potential mechanisms whereby viral infections may amplify the development of fibrosis. While none of these studies prove causality, we believe the evidence suggests that viral infections should be considered as potential initiators or exacerbating agents in at least some cases of IPF and thereby justify further study.
特发性肺纤维化（IPF）的病因仍不明朗。该疾病的起源原因未知，其发病机制也鲜为人知。虽然该疾病可能是多因素导致的，但越来越多的证据表明病毒是纤维化肺病的辅助因素（无论是作为起始因素还是加重因素）。本综述总结了现有的临床和实验观察结果，这些结果构成了病毒感染可能增强纤维化反应这一假说的基础。我们回顾了表明丙型肝炎病毒、腺病毒、人巨细胞病毒，特别是爱泼斯坦 - 巴尔γ疱疹病毒与IPF之间存在联系的数据。此外，我们强调了γ疱疹病毒感染与马肺纤维化之间最近建立的关联，并讨论了用于研究γ疱疹病毒对纤维化进展贡献的各种小鼠模型。我们回顾了表明偏向Th2的小鼠感染γ疱疹病毒会导致多器官纤维化的研究，并强调了显示在纤维化挑战之前或之后感染γ疱疹病毒的小鼠会加剧纤维化发展的研究。最后，我们讨论了病毒感染可能放大纤维化发展的潜在机制。虽然这些研究都没有证明因果关系，但我们认为证据表明，在至少某些IPF病例中，病毒感染应被视为潜在的起始因素或加重因素，因此有理由进行进一步研究。
