Hou X Q, Qin J L, Zheng X X, Wang L, Yang S T, Gao Y W, Xia X Z H
Acta Virol. 2014;58(1):69-75. doi: 10.4149/av_2014_01_69.
During influenza A virus (IAV) (H5N1) infection, the levels of inflammatory cytokines are markedly elevated in the lungs of infected hosts. One of them, high-mobility group box 1 protein (HMGB1) functions in regulation of cellular transcription and activation of proinflammatory responses, but little is known about its role in viral infection. In this study, we attempted to address this question. Using an IAV (H5N1) - mouse model, lung tissues were analyzed for virus titer, expression of HMGB1 and other inflammatory cytokines and histopathological changes. Moreover, the effect of administration of HMGB1-specific antibody to the infected mice on these parameters was investigated. The results showed that the HMGB1 expression was induced on days 3-7 post infection (p.i.) and primarily localized to epithelial cells of alveoli and bronchioles. The HMGB1-specific antibody reduced the levels of inflammatory cytokines and chemokines and the survival rate, but did not influence the virus titer. Summing up, these data suggest that HMGB1 contributes to the pathogenesis of IAV (H5N1) infection in mice by inducing extensive inflammatory responses and severe pneumonia.
在甲型流感病毒（IAV）（H5N1）感染期间，受感染宿主肺部的炎性细胞因子水平显著升高。其中之一，高迁移率族蛋白B1（HMGB1）在细胞转录调控和促炎反应激活中发挥作用，但对其在病毒感染中的作用知之甚少。在本研究中，我们试图解决这个问题。使用IAV（H5N1）-小鼠模型，分析肺组织中的病毒滴度、HMGB1和其他炎性细胞因子的表达以及组织病理学变化。此外，还研究了给感染小鼠注射HMGB1特异性抗体对这些参数的影响。结果显示，感染后第3至7天诱导了HMGB1表达，且主要定位于肺泡和细支气管的上皮细胞。HMGB1特异性抗体降低了炎性细胞因子和趋化因子水平以及存活率，但不影响病毒滴度。总之，这些数据表明，HMGB1通过诱导广泛的炎性反应和严重肺炎，在小鼠IAV（H5N1）感染的发病机制中发挥作用。
