Chan M C W, Cheung C Y, Chui W H, Tsao S W, Nicholls J M, Chan Y O, Chan R W Y, Long H T, Poon L L M, Guan Y, Peiris J S M
Department of Microbiology, The University of Hong Kong, Queen Mary Hospital, Hong Kong Special Administrative Region of China.
Respir Res. 2005 Nov 11;6(1):135. doi: 10.1186/1465-9921-6-135.
Fatal human respiratory disease associated with influenza A subtype H5N1 has been documented in Hong Kong, and more recently in Vietnam, Thailand and Cambodia. We previously demonstrated that patients with H5N1 disease had unusually high serum levels of IP-10 (interferon-gamma-inducible protein-10). Furthermore, when compared with human influenza virus subtype H1N1, the H5N1 viruses in 1997 (A/Hong Kong/483/97) (H5N1/97) were more potent inducers of pro-inflammatory cytokines (e.g. tumor necrosis factor-a) and chemokines (e.g. IP-10) from primary human macrophages in vitro, which suggests that cytokines dysregulation may play a role in pathogenesis of H5N1 disease. Since respiratory epithelial cells are the primary target cell for replication of influenza viruses, it is pertinent to investigate the cytokine induction profile of H5N1 viruses in these cells.
We used quantitative RT-PCR and ELISA to compare the profile of cytokine and chemokine gene expression induced by H5N1 viruses A/HK/483/97 (H5N1/97), A/Vietnam/1194/04 and A/Vietnam/3046/04 (both H5N1/04) with that of human H1N1 virus in human primary alveolar and bronchial epithelial cells in vitro.
We demonstrated that in comparison to human H1N1 viruses, H5N1/97 and H5N1/04 viruses were more potent inducers of IP-10, interferon beta, RANTES (regulated on activation, normal T cell expressed and secreted) and interleukin 6 (IL-6) in primary human alveolar and bronchial epithelial cells in vitro. Recent H5N1 viruses from Vietnam (H5N1/04) appeared to be even more potent at inducing IP-10 than H5N1/97 virus.
The H5N1/97 and H5N1/04 subtype influenza A viruses are more potent inducers of proinflammatory cytokines and chemokines in primary human respiratory epithelial cells than subtype H1N1 virus. We suggest that this hyper-induction of cytokines may be relevant to the pathogenesis of human H5N1 disease.
与甲型H5N1流感病毒相关的人类致命呼吸道疾病已在香港有记录，最近在越南、泰国和柬埔寨也有发现。我们之前证明，感染H5N1病毒的患者血清中IP - 10（γ干扰素诱导蛋白10）水平异常高。此外，与人类甲型H1N1流感病毒相比，1997年的H5N1病毒（A/香港/483/97）（H5N1/97）在体外能更有效地诱导原代人巨噬细胞产生促炎细胞因子（如肿瘤坏死因子 - α）和趋化因子（如IP - 10），这表明细胞因子失调可能在H5N1疾病的发病机制中起作用。由于呼吸道上皮细胞是流感病毒复制的主要靶细胞，因此研究H5N1病毒在这些细胞中的细胞因子诱导谱是有意义的。
我们使用定量逆转录聚合酶链反应（qRT - PCR）和酶联免疫吸附测定（ELISA），在体外比较H5N1病毒A/香港/483/97（H5N1/97）、A/越南/1194/04和A/越南/3046/04（均为H5N1/04）与人类H1N1病毒在原代人肺泡和支气管上皮细胞中诱导细胞因子和趋化因子基因表达的情况。
我们证明，与人类H1N1病毒相比，H5N1/97和H5N1/04病毒在体外能更有效地诱导原代人肺泡和支气管上皮细胞产生IP - 10、β干扰素、调节激活正常T细胞表达和分泌因子（RANTES）和白细胞介素6（IL - 6）。来自越南的近期H5N1病毒（H5N1/04）在诱导IP - 10方面似乎比H5N1/97病毒更有效。
H5N1/97和H5N1/04亚型甲型流感病毒比H1N1亚型病毒更能有效地诱导原代人呼吸道上皮细胞产生促炎细胞因子和趋化因子。我们认为这种细胞因子的过度诱导可能与人类H5N1疾病的发病机制有关。
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