格尔德霉素体内抑制高致病性禽流感病毒H5N1增殖  

Geldanamycin reduces proliferation of highly pathogenic H5N1 avian influenza virus in vivo

作　　者：刘朋朋[1,2] 胡奕[2,3] 赵宝华[3] 仲飞[1] 何宏轩[2] 

机构地区：[1]河北农业大学动物医学院,农业部动物疫病病原生物学华北科学观察实验站,保定071001 [2]中国科学院动物研究所,国家野生动物疫病研究中心,北京100101 [3]河北师范大学生命科学学院,石家庄050016

出　　处：《科学通报》2013年第11期1021-1026,共6页Chinese Science Bulletin

基　　金：中国科学院知识创新工程(KSCX2-YW-N-063);USDA-IOZ CAS中美合作项目(O760621234);国家科技支撑计划(2009BAI83B01);国家自然科学基金(31072126/C1804;31101806/C1804)资助

摘　　要：为了评价Hsp90抑制剂——格尔德霉素体内抗流感病毒的效果,利用高致病性禽流感病毒H5N1鼠适应株感染小鼠,分析格尔德霉素对流感病毒H5N1感染小鼠的死亡保护率以及不同时相肺部病毒负载量的影响.本实验用乙醚麻醉小鼠,流感病毒H5N1滴鼻感染C57BL/6小鼠,于感染后2h腹腔注射格尔德霉素,观察小鼠死亡保护率、体重变化及Real-time PCR检测小鼠肺部病毒负载量.生存分析结果显示格尔德霉素治疗组(80%)与对照组(3%)及奥司他韦治疗组(53%)相比极显著(P<0.01)地延长了流感病毒感染小鼠存活率及存活时间,且平均体重丢失也少于对照组及奥司他韦治疗组;Real-time PCR分析显示格尔德霉素极显著(P<0.01)地抑制了流感病毒H5N1的复制,与奥司他韦治疗组无显著性差异(P>0.05).上述实验结果显示格尔德霉素对流感病毒H5N1感染的小鼠提供了很好的保护作用,且显著抑制了流感病毒H5N1的增殖,可能作为一种新的、高效的抗流感病毒备选药物.To evaluate the anti-influenza activity of the Hsp90 inhibitor Geldanamycin, mice were infected with mouse-adapted influenza virus A/environment/Qinghai/1/2008（H5N1）, and treated with Geldanamycin. Mice were infected intranasally with 2~105 pfu influenza virus H5N1 under etherization, and survival time and lung viral load were monitored. Experimental groups were administered Geldanamycin intraperitoneally 2 h following infection, and survival time and weight change were observed up to 12 d after infection. Real-time PCR was used to measure viral load on days 2, 4, and 7. Survival analysis showed that Geldanamycin administration significantly prolonged survival （80%） compared with control （3%）, and was more efficient than Oseltamivir （53%）. Viral load levels suggested that Geldanamycin significantly reduced viral replication compared with control （P〈0.01）, but was not significantly different compared with Oseltamivir-treated （P〉0.05）. These results indicate that mice infected with influenza virus H5N1 are protected by Geldanamycin administration, which significantly inhibited viral replication. Geldanamycin may potentially serve as a novel, highly effective anti-influenza drug.

关 键 词：高致病性禽流感病毒H5N1 格尔德霉素 死亡保护率 病毒负载量 

分 类 号：S852.65[农业科学—基础兽医学]