Hsp90抑制剂CH5138303抗轮状病毒感染的作用研究  

Roles of Hsp90 inhibitor CH5138303 in anti-rotavirus infection

作　　者：祝庆民 李晋涛 吴玉章 何海洋 ZHU Qingmin;LI Jintao;WU Yuzhang;HE Haiyang(Team 13 of the Fourth Brigade,Basic Medical School,Army Military University,Chongqing 400038,China;Department of Biosafety,Basic Medical School,Army Military University,Chongqing 400038,China;Department of Immunology,Basic Medical School,Army Military University,Chongqing 400038,China)

机构地区：[1]陆军军医大学基础医学院学员四大队13队,重庆400038 [2]陆军军医大学基础医学院生物安全教研室,重庆400038 [3]陆军军医大学基础医学院免疫学教研室,重庆400038

出　　处：《免疫学杂志》2023年第1期21-27,共7页Immunological Journal

基　　金：基础研究与前沿探索重点项目(cstc2015jcyjBX0086)。

摘　　要：目的研究Hsp90抑制剂CH5138303在抗轮状病毒感染中的作用。方法使用人肠上皮细胞Caco-2感染轮状病毒Wa株模型评价CH5138303对轮状病毒感染的作用,流式细胞术评价CH5138303抑制轮状病毒Wa株感染肠上皮细胞Caco-2感染效率;同时通过检测新生病毒的滴度评价高、低浓度(10μmol/L、1μmol/L)CH5138303抑制活性轮状病毒的生成效果;进一步,使用乳鼠体内实验,评价口服CH5138303抑制轮状病毒感染导致腹泻发生程度及重症致死性轮状病毒感染的死亡率。结果(1)CH5138303显著抑制轮状病毒感染建立;(2)CH5138303强烈抑制活性轮状病毒的生成;(3)不同浓度(10μmol/L、1μmol/L)CH5138303抑制效率分别为90%及80%;(4)CH5138303显著缓解轮状病毒乳鼠腹泻症状;(5)CH5138303显著降低重症致死性轮状病毒感染模型中小鼠死亡率;(6)CH5138303细胞毒性较常见的Hsp90抑制剂格尔德霉素、17-AAG显著较低。结论Hsp90抑制剂CH5138303能显著抑制轮状病毒复制,延缓轮状病毒腹泻的发生,特别是有效的降低重症致死性轮状病毒腹泻的发生,从而有助于高效特异性抗轮状病毒药物的开发。To study the roles of Hsp90 inhibitor CH5138303 in anti-rotavirus infection,a model of human intestinal epithelial cell Caco-2 infecting with rotavirus Wa strain was established.Flow cytometry was used to evaluate roles of CH5138303 in Caco-2 infection by rotavirus Wa strain.Also,the inhibitory effect of different concentrations(10μmol/L,1μmol/L)of CH5138303 on active rotavirus production was evaluated by detecting the titer of newborn virus.Furthermore,the in vivo experiment of suckling mice was carried out to evaluate the inhibitory effect of oral CH5138303 on the incidence of diarrhea caused by rotavirus infection and the mortality of severe lethal rotavirus infection.Data showed that CH5138303 significantly inhibited rotavirus infection;CH5138303 also strongly inhibits the production of active rotavirus,and the inhibition efficiency of CH5138303 at different concentrations(10μmol/L and 1μmol/L)was 90%and 80%,respectively.In vivo experiment indicated that CH5138303 significantly relieved the diarrhea symptoms of rotavirus suckling mice,and significantly reduced the mortality of mice with severe lethal rotavirus infection.The cytotoxicity of CH5138303 was significantly lower than those of Geldanamycin and 17-AAG.Taken together,the Hsp90 inhibitor CH5138303 can significantly inhibit the replication of rotavirus,delay the occurrence of rotavirusdiarrhea,and effectively reduce the occurrence of severefatal rotavirus diarrhea,thus contributing to thedevelopment of highly specific anti-rotavirus drugs.

关 键 词：HSP90 CH5138303 轮状病毒 腹泻 

分 类 号：R392.1[医药卫生—免疫学]