Induction of proinflammatory cytokines in human macrophages by influenza A (H5N1) viruses: a mechanism for the unusual severity of human disease?
Induction of proinflammatory cytokines in human macrophages by influenza A (H5N1) viruses: a mechanism for the unusual severity of human disease?
复制标题
DOI：
10.1016/s0140-6736(02)11772-7
复制
发表时间：
2002-12-07
期刊：
影响因子：
168.9
通讯作者：
Peiris, JSM
中科院分区：
文献类型：
--
作者：
Cheung, CY;Poon, LLM;Peiris, JSM
背景在1997年，与纯粹的鸟类H5N1流感病毒相关的人类呼吸道疾病和死亡的第一个记录实例导致总体病例效率为33％。人类H5N1疾病严重程度的生物学基础尚不清楚。我们测试了病毒诱导的细胞因子失调的假设。方法我们使用了cDNA阵列和定量RT-PCR来比较病毒A/HK/HK/486/97和A/HK/HK/HK/483/483/483/483/483/483/483/483/483/483/483/483/483/483/483/483/483/483/483/483/483/483/483/483/483/483/483/483/483/ 97（H5N1/97）与人类原发性中的人类H3N2和H1N1病毒的97（H5N1/97）单核细胞衍生的巨噬细胞体外。 ELISA比较了感染病毒的巨噬细胞的肿瘤坏死因子α（TNFα）的分泌。通过使用反向遗传技术产生的天然发生的病毒性替代品和重组病毒，我们研究了与TNF-Alpha反应相关的病毒基因。调查H5N1/97病毒引起的H3N2或H1N1 VIRUSES，诱导的H5N1/97病毒诱导了更高的促炎细胞因子基因转录。特别是TNF alpha。和干扰素beta。 TNF-α的浓度。被这些病毒感染的巨噬细胞培养上清液中的蛋白质类似于大肠杆菌脂多糖刺激引起的蛋白质。 H5N1/97病毒的非结构性（NS）基因段有助于该病毒诱导的TNFα的增加。诠释H5N1/97病毒是巨噬细胞中促炎细胞因子的有效诱导剂，是巨噬细胞中巨噬细胞的有效诱导剂，是最著名的是TNF Alpha。这种特征可能导致人类H5N1疾病的异常严重程度。
Background In 1997, the first documented instance of human respiratory disease and death associated with a purely avian H5N1 influenza virus resulted in an overall case-fatality rate of 33%. The biological basis for the severity of human H5N1 disease has remained unclear. We tested the hypothesis that virus-induced cytokine dysregulation has a role.Methods We used cDNA arrays and quantitative RT-PCR to, compare the profile of cytokine gene expression induced by viruses A/HK/486/97 and A/HK/483/97 (both H5N1/97) with that of human H3N2 and H1N1 viruses in human primary monocyte-derived macrophages in vitro. Secretion of tumour necrosis factor alpha (TNF alpha) from macrophages infected with the viruses was compared by ELISA. By use of naturally occurring viral reassortants and recombinant viruses generated by reverse genetic techniques, we investigated the viral genes associated with the TNF-alpha response.Findings The H5N1/97 viruses induced much higher gene transcription of proinflammatory cytokines than did H3N2 or H1N1 viruses, particularly TNF alpha. and interferon beta. The concentration of TNF-alpha. protein in culture supernatants of macrophages infected with these viruses was similar to that induced by stimulation with Escherichia coli lipopolysaccharide. The non-structural (NS) gene-segment of H5N1/97 viruses contributed to the increase in TNF alpha induced by the virus.Interpretation The H5N1/97 viruses are potent inducers of proinflammatory cytokines in macrophages, the most notable being TNF alpha. This characteristic may contribute to the unusual severity of human H5N1 disease.