Hardarson Hordur S, Baker J Scott, Yang Zhao, Purevjav Enkhsaikhan, Huang Chien-Hua, Alexopoulou Lena, Li Na, Flavell Richard A, Bowles Neil E, Vallejo Jesus G
Department of Pediatrics, Section of Infectious Diseases, Baylor College of Medicine and Texas Children's Hospital, Houston, Texas 77030, USA.
Am J Physiol Heart Circ Physiol. 2007 Jan;292(1):H251-8. doi: 10.1152/ajpheart.00398.2006. Epub 2006 Aug 25.
Enterovirus-induced myocardial injury can lead to severe heart failure. To date, little is known about the early innate stress response that contributes to host defense in the heart. Toll-like receptor 3 (TLR3) is important in the initiation of the innate antiviral response. We investigated the involvement of TLR3, which recognizes viral double-stranded RNA, on encephalomyocarditis virus (EMCV) infection. To examine the contribution of TLR3 in protection from EMCV infection, we infected mice deficient in TLR3 with 50 plaque-forming units of EMCV. TLR3-deficient (TLR3(-/-)) mice were more susceptible to EMCV infection and had a significantly higher viral load in the heart compared with TLR3(+/+) mice. Histopathological examination showed that the inflammatory changes of the myocardium were less marked in TLR3(-/-) than in TLR3(+/+)mice. TLR3(-/-) mice had impaired proinflammatory cytokine and chemokine expression in the heart following EMCV infection. However, the expression of interferon-beta was not impaired in EMCV-infected TLR3(-/-) mice. EMCV infection leads to a TLR3-dependent innate stress response, which is involved in mediating protection against virus-induced myocardial injury.
肠道病毒引起的心肌损伤可导致严重心力衰竭。迄今为止，人们对有助于心脏宿主防御的早期先天性应激反应知之甚少。Toll样受体3（TLR3）在先天性抗病毒反应的启动中起重要作用。我们研究了识别病毒双链RNA的TLR3在脑心肌炎病毒（EMCV）感染中的作用。为了研究TLR3在抵御EMCV感染中的作用，我们用50个噬斑形成单位的EMCV感染了TLR3基因缺陷的小鼠。与TLR3(+/+)小鼠相比，TLR3基因缺陷（TLR3(-/-)）小鼠对EMCV感染更敏感，心脏中的病毒载量显著更高。组织病理学检查显示，TLR3(-/-)小鼠心肌的炎症变化比TLR3(+/+)小鼠轻。EMCV感染后，TLR3(-/-)小鼠心脏中的促炎细胞因子和趋化因子表达受损。然而，EMCV感染的TLR3(-/-)小鼠中干扰素-β的表达未受损。EMCV感染导致TLR3依赖性先天性应激反应，该反应参与介导对病毒诱导的心肌损伤的保护作用。
