日本腦炎病毒(Japanese encephalitis virus, JEV)複製受細胞自噬負向調控且發生於含LC3-I及EDEM-1的膜上 Japanese encephalitis virus replication is negatively regulated by autophagy and occurs on LC3-I- and EDEM1-containing membranes

Manish S., Sankar B., Minu N., Manpreet K., Vikas S., Vishal G., Renu K., Malik Z A., Sudhanshu V. & Manjula K., Autophagy (2014) 10(9):1637-51  

Speaker講者: Po-Jung Fu (傅柏蓉)                                 　　　　　　　　                                                Time時間: 15:00~16:00, Apr, 2015.

Commentator講評者: Dr. Guey-Chuen Perng (彭貴春 老師)               　　　　　　　　　　　　　                                  Place地點: Room 601教室

Abstract摘要:

     正股RNA病毒[(+) RNA]會利用宿主因子形成病毒複製複合物Positive sense RNA [(+) RNA] viruses subvert host factors to form virus replication complex (VRC). VRC 匯集濃縮縮病毒急宿主因子以加速病毒本身RNA形成並保護病毒免於被宿主免疫系統辨認concentrates virus and host factors to facilitate virus RNA synthesis and protects virus from recognizing by host immune system [1]．. 冠狀病毒(Coronaviruses ,(CoV)會將內質網(endoplasimic reticulum ,ER) 的膜重新塑形以形成雙層膜載體(double membrane vesicle ,DMV)．remodels endoplasimic reticulum (ER) membrane to form a double membrane vesicle (DMV). CoVv　將其複製及轉錄因子轉位（translocases）到 translocases 此DMV中its replication and transcription factors to the DMV. [2]．. The DMV 形成會擾亂維持內質網恆定的過程，此過程稱為內質網相關的降解調諧[ER-associating degradation (ERAD) tuning]．在正常情況下，EDEM-1(為一重要的ERAD調節子)會自內質網被送到含有LC3-1的小胞快速進行降解(此小胞稱為EDEMOsome)以維持EDEM-1低濃度．formation resultsing in CoV interference of ER-associating degradation (ERAD) tuning, which is a process to maintain ER at steady state. Under normal growth conditions, EDEM-1, a crucial regulator of ERAD, was segregated from bulk ER to LC3-Ⅰcontaining vesicle (known as EDEMOsomes)然而， and rapidly degraded to keep EDEM-1at the low level of EDEM-1. However, (+) RNA viruses病毒盜用此一路徑形成 hijack this pathway to form DMV作為病毒複製的平台．, which serves as virus replication platform.

     Japanese encephalitis virus (JEV是一) is a (+) RNA virus and belongs to Flaviviridae.病毒，隸屬黃熱病毒科．此病毒會引起嚴重的神經感染． It causes severe neurologic manifestation.雖然疫苗可以提供有效的預防，但地區性或全區性的爆發仍然使有所聞． Although vaccination is efficient way to prevent disease, epidemic or endemic outbreak still occurs. JEV 的致死率大約是The fatality of JEV ranges from 20% ~to 30%, 神經性後遺症發生率在with neurologic or psychiatric sequelae observed in 30~50%的存活者 survivors [4].在此篇報導中，作者他們發現JEV感染的神經細胞中， In this paper,細胞自噬缺乏會增加病毒的複製及細胞對病毒感染的感受性．他們進一步的發現顯示JEV複製複合物與EDEMOsomes有關，此一結果與其他已報導的(+) RNA相似． the authors found that in JEV infected neuronal cells, autophagy deficiency increased viral replication and cell susceptibility to virus infection. 然而，此病毒複製複合物並不與Their further study showed n that JEV replication complex associates with EDEMOsomes, which is similar to the report on other (+) RNA viruses. LC3-GFPHowever, the virus replication complex did not colocalize with LC3-GFPco-localize，而LC3-GFP被認為可代表自噬小體上的LC3-II,．總結來說，此篇報導指出1.  which represents autophagosome LC3-Ⅱ. In conclusion, this paper suggests that 1. JEV 感染會誘發細胞自噬現象，此一現象負向條控病毒複製infection induces autophagy which negatively regulates virus replication, 2. JEV利用裝飾有LC3-I的EDEMOsome來做為他的複製平台． utilizes JEV utilizes EDEMosomes that decorated with LC3-Ⅰprotein as replication complex.

EDEMosomes that and decorate themd with LC3-Ⅰ protein as replication complex.

References參考資料:

1.    Nagy, P.D. and Pogany J., The dependence of viral RNA replication on co-opted host factors. Nat Rev Microbiol (2012) 10(2): 137-49.

2.    Reggiori, F., de Haan C. A., and Molinari M., Unconventional use of LC3 by coronaviruses through the alleged subversion of the ERAD tuning pathway. Viruses (2011) 3(9): 1610-23.

3.    Cali, T., Galli, C., Olivari, S. and Molinari, M., Segregation and rapid turnover of EDEM1 by an autophagy-like mechanism modulates standard ERAD and folding activities. Biochem Biophys Res Commun, 2008. 371(3): 405-10.

4.    Wang, H. and Liang G., Epidemiology of Japanese encephalitis: past, present, and future prospects. Ther Clin Risk Manag (2015) 11: 435-48.