Proteomic methods reveal cyclophilin a function as a host restriction factor against rotavirus infection
Proteomic methods reveal cyclophilin a function as a host restriction factor against rotavirus infection
复制标题
蛋白质组学方法揭示亲环蛋白作为抗轮状病毒感染的宿主限制因子的功能
DOI：
10.1002/pmic.201100579
复制
发表时间：
2013-04-01
期刊：
影响因子：
3.4
通讯作者：
Wu, Yuzhang
中科院分区：
文献类型：
--
作者：
He, Haiyang;Mou, Zhirong;Wu, Yuzhang
轮状病毒(RV)感染是全球5岁以下婴幼儿急性脱水腹泻的主要原因。与许多其他病毒一样，轮状病毒感染会导致宿主蛋白的全球关闭。然而，以往的研究表明，轮状病毒可以选择性地上调某些宿主蛋白的表达，从而在轮状病毒感染中发挥重要作用。为了在全球范围内发掘在早期人类轮状病毒(HRV)感染中上调的宿主蛋白，我们使用蛋白质组学方法，明确地鉴定了10种上调的宿主蛋白。亲环素A(Cyclophin A，CyPA)是一种肽基-脯氨基顺反异构酶，是上调表达的宿主蛋白之一。在感染后，CyPA被招募到病毒质中并与HRV结构蛋白VP2相互作用；CyPA通过抑制病毒蛋白的表达降低了宿主对HRV感染的敏感性，并抑制了HRV的复制。此外，我们还发现在BALB/c小鼠对轮状病毒腹泻产生抵抗力的时间段内，肠上皮细胞CyPA的表达增加。总之，我们确定CyPA是一种新的宿主限制因子，对RV感染具有保护作用，并可能有助于宿主对RV腹泻的易感性。
Rotavirus (RV) infection is the main cause of acute dehydrating diarrhea in infants and young children below 5 years old worldwide. RV infection causes a global shutoff of host proteins as many other viruses do. However, previous studies revealed that RV could selectively upregulated the expression of some host proteins that then played important roles in RV infection. To globally explor such host proteins that were upregulated in early human rotavirus (HRV) infection, proteomic methods were used and a total of ten upregulated host proteins were unambiguously identified. Cyclophilin A (CYPA), a peptidyl-prolyl cis-trans isomerase, was among these upregulated host proteins. Following infection, CYPA was recruited to the viroplasm and interacted with HRV structural protein VP2; CYPA reduced host susceptibility to HRV infection and inhibited replication of HRV by repressing the expression of viral proteins. Furthermore, we found that the increased expression of CYPA in enterocytes of small intestine correlated to the period when BALB/c mice became resistant to RV diarrhea. Together, we identified CYPA as a novel host restriction factor that confered protection against RV infection and might contribute to host susceptibility to RV diarrhea.