The molecular chaperone heat shock protein-90 positively regulates rotavirus infectionx
The molecular chaperone heat shock protein-90 positively regulates rotavirus infectionx
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DOI：
10.1016/j.virol.2009.06.044
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发表时间：
2009-09-01
期刊：
影响因子：
3.7
通讯作者：
Chawla-Sarkar, Mamta
中科院分区：
文献类型：
--
作者：
Dutta, Dipanjan;Bagchi, Parikshit;Chawla-Sarkar, Mamta
轮状病毒是全球儿童严重脱水胃肠炎的主要原因。在这项研究中，我们报告了细胞伴侣Hsp90在轮状病毒感染过程中的积极作用。用高度特异的Hsp90抑制剂17-烯丙氨基去甲氧基格尔达那霉素(17-AAG)来描述Hsp90的功能作用。在病毒吸附后用17-AAG处理的MA104细胞中，通过对空斑形成单位和病毒基因表达的定量评估，抑制了猴(SA11)或人(KU)株的复制。SA11与2-4HPI观察到Akt和核因子kappaB的磷酸化，在17-AAG存在下，Akt和NF kappa B的磷酸化被强烈抑制。病毒感染细胞中Hsp90-Akt的直接相互作用在17-AAG存在时也被减少。17-AAG的抗轮状病毒作用是由于抑制了Akt的激活，PI3K/Akt抑制剂显著抑制了轮状病毒的生长。因此，Hsp90通过调节细胞信号蛋白来调节轮状病毒。这些结果突出了细胞蛋白在轮状病毒感染过程中的重要性，以及靶向细胞伴侣蛋白用于开发新的抗轮状病毒策略的可能性。(C)2009 Elsevier Inc.保留所有权利。
Rotaviruses are the major cause of severe dehydrating gastroenteritis in children Worldwide. In this study, we report a positive role of cellular chaperone Hsp90 during rotavirus infection. A highly specific Hsp90 inhibitor, 17-allylamono-demethoxygeldanamycin (17-AAG) was used to delineate the functional role of Hsp90. In MA104 cells treated with 17-AAG after viral adsorption, replication of simian (SA11) or human (KU) strains was attenuated as assessed by quantitating both plaque Forming units and expression of viral genes. Phosphorylation of Akt and NF kappa B observed 2-4 hpi with SA11, was strongly inhibited in the presence of 17-AAG. Direct Hsp90-Akt interaction in virus infected cells was also reduced in the presence of 17-AAG. Anti-rotaviral effects of 17-AAG were due to inhibition of activation of Akt that was confirmed since, PI3K/Akt inhibitors attenuated rotavirus growth significantly. Thus, Hsp90 regulates rotavirus by modulating cellular signaling proteins. The results highlight the importance of cellular-proteins during rotavirus infection and the possibility of targeting cellular chaperones for developing new anti-rotaviral strategies. (C) 2009 Elsevier Inc. All rights reserved.