Wortmannin delays transfer of human rhinovirus serotype 2 to late endocytic compartments
Wortmannin delays transfer of human rhinovirus serotype 2 to late endocytic compartments
复制标题
DOI：
10.1016/j.bbrc.2006.07.125
复制
发表时间：
2006-09-22
影响因子：
3.1
通讯作者：
Fuchs, Renate
中科院分区：
文献类型：
--
作者：
Brabec, Marianne;Blaas, Dieter;Fuchs, Renate
人鼻病毒2（HRV 2）被低密度脂蛋白受体家族成员内化到早期内体（pH 6.2-6.0）中，在此与其受体解离。在转移到晚期内体中后，病毒经历构象变化，并且RNA脱壳仅由pH < 5.6诱导。最后，病毒衣壳在溶酶体中降解。为了研究磷脂酰肌醇3-激酶（PI 3 K）在HRV 2进入途径中的作用，我们使用了抑制剂渥曼青霉素。虽然渥曼青霉素没有改变病毒的内化，但病毒在扩大的早期内体中积累。此外，该药物延迟了HRV 2降解和病毒蛋白合成。因此，渥曼青霉素敏感的PI 3 K参与了HRV 2从早期到晚期的运输。但渥曼青霉素对所产生的感染性病毒滴度无影响。因此，我们的数据表明，在早期内体中保留较长时间的病毒可以经历在晚期内体中在pH < 5.6时发生的构象变化。(c)2006年爱思唯尔公司All rights reserved.
Human rhinovirus 2 (HRV2) is internalized by members of the low-density lipoprotein receptor family into early endosomes (pH 6.2-6.0) where it dissociates from its receptors. After transfer into late endosomes, the virus undergoes a conformational change and RNA uncoating solely induced by pH < 5.6. Finally, virus capsids are degraded in lysosomes. To investigate the role of phosphatidylinositol 3-kinases (PI3K) in the HRV2 entry route, we used the inhibitor wortmannin. Although virus internalization was not altered by wortmannin, virus accumulated in enlarged early endosomes. Furthermore, the drug delayed HRV2 degradation and viral protein synthesis. Consequently, wortmannin-sensitive PI3K are involved in HRV2 transport from early to late compartments. However, wortmannin had no effect on the titer of infectious virus produced. Our data therefore suggest that virus retained in early endosomes for prolonged time periods can undergo the conformational change that otherwise occurs at pH < 5.6 in late endosomes. (c) 2006 Elsevier Inc. All rights reserved.