格尔德霉素抑制高致病性禽流感病毒增殖及其所介导炎性反应研究

Inhibition of Highly Pathogenic Avian Influenza A Virus H5N1 Growth and Induction of Inflammatory Mediators by Geldanamycin

对高致病性禽流感病毒感染最为有效的治疗应采用抗病毒和抗炎症的联合治疗.本试验用流感病毒H5N1感染不同细胞株(A549细胞和MDCK细胞),采用不同浓度格尔德霉素对病毒感染细胞培养物作用不同时长,检测流感病毒滴度;ELISA检测格尔德霉素作用于流感病毒H5N1感染A549细胞12 h、24 h促炎性细胞因子IFN-α、TNF-α和IL-6水平.结果显示,流感病毒H5N1感染A549细胞和MDCK细胞,格尔德霉素极显著地抑制了流感病毒H5N1在细胞培养物的增殖(P<0.01),而在病毒感染36 h和48 h,格尔德霉素并没有显著抑制流感病毒在MDCK细胞上的增殖(P>0.05).促炎性细胞因子分析结果显示,格尔德霉素在流感病毒感染A549细胞12 h和24 h均显著降低了促炎性细胞因子IFN-α、TNF-α和IL-6的分泌(P<0.05).上述实验结果显示,格尔德霉素具有抑制流感病毒H5N1增殖及其所介导的炎性反应的双重效应,为格尔德霉素成为应对流感病毒流行的备选药物提供基础科学依据.

Better effective therapy for highly pathogenic influenza virus infection should consist of combinations of an effective antiviral agent and immunomodulatory agents to control viral replication and pulmonary injury, respectively. Here we evaluated the virus titres in different cells （A549 cells and MDCK cells） infected with influenza virus H5N1 by plaque assay with the various concentrations of Geldanamycin at different time points. The levels of proinflammatory cytokines from A549 cell infected with influenza virus H5Nlwere detected by ELISA in the absence or presence of Geldanamycin. Our findings showed that Geldanamycin significantly inhibited influenza virus growth in MDCK cells and A549 cells（P 〈 0.01）. However, influenza virus growth were not inhibited with Geldanamycin on 36 h and 48 h（P 〉 0.05）after infection with influenza virus H5N1. Analysis of proinflammatory cytokines in Geldanamycin-treated A549 cells revealed significant reductions in IFN-α, TNF-α or IL-6 on 12 h and 24 h after infection with influenza virus H5N1 （/9 〈 0.05）. All the results indicated that Geldanamycin have the dual effect of combine antivirus with anti-inflammation, which provided the science data for the potential use of Geldanamycin as a novel, highly effective anti-influenza virus drug.