Leukocyte immunoglobulin-like 受器(Leukocyte immunoglobulin-like receptor) B1在抗體依賴增強現象(antibody dependent enhancement)感染的登革疾病扮演重要角色 is critical for antibody-dependent dengue

Kuan Rong Chan, Eugenia Z. Ong, Hwee Cheng Tan, Summer Li-Xin Zhang, Qian Zhang, Kin Fai Tang, Nivashini Kaliaperumal, Angeline Pei Chiew Lim, Martin L. Hibberd, Soh Ha Chan, John E. ConnollyManoj N. Krishnan, Shee Mei Lok, Brendon J. Hanson, Chao-Nan Lin, and Eng Eong Ooi. PNASProc NatlAcad Sci USA. 111(7)1:, 2722-2727 (2014)

Speaker: Po-Jung Fu (傅柏蓉)               )                                              Time: 13:00~14:00, May 28, 2014.

Commentator: DRDr. Guey-Chuen Perng (彭貴春 老師)         )       Place: Room 6015761 (Medical Laboratory Science and Biotechnology, 3F)

Abstract:

   登革病毒(Dengue virus，DENV)是一單股RNA病毒，屬於黃熱病毒科黃熱病毒屬，經由斑蚊傳播，每年引起三十九億人感染．二次遭受到不同血清型的病毒感染會使得病毒可藉由Fc-gamma 受器(Fc-gamma receptor ，FcR)進入具此受器的細胞，例如巨噬細胞(Dengue virus (DENV)macrophagy )、單核球(monocyte)及樹突狀細胞(dendricted cell)，此現象稱為抗體依賴增強現象(antibody-dependent enhancement，ADE) is a single-stranded ssRNA virus, belonging to Flaviviridae, transmitted by Aedes spp. mosquitoes and causes 390 million infectionsannually. Secondary infection with hetero serotype of DENV will increases virus entry into Fc-gamma receptor (Fc��R) bearing cell, monocyte, macrophagy and dendricted cells, and this phenomenon is known as antibody-dependent enhancement (ADE) of DENV infection [1]. Severe dengue disease,由登革病毒引起的重症，如登革出血熱( dengue hemorrhagic fever (，DHF)and 及登革休克症狀(dengue shock syndrome ，(DSS) were are closely related to 都與ADE有密切的關連，因為ADE會使得病毒量增加並增加宿主全身性的發炎反應． because of the resultantwhich results in greater increased viral burden to increase systemic inflammatio有趣的是，此一透過Fc-gamma 受器的增強現象，會藉由第一型干擾素刺激基因(type-I IFN-stimulated genes ，ISGs)表現而誘發誘導抗病毒訊號的產生n. ．Intriguingly, in the previous study, this enhancement of DENV infection will activates early Fc��R early anti-virus signals by through inducing the type-I IFN-stimulated genes (ISGs).

   在此篇文獻中，作者利用單核球THP-1細胞，證明登革病毒如何逃脫由Fc-gamma 受器誘導產生的抗病毒反應．In this paper, the authors used the monocyte THP-1 cells to demonstrate that tohow DENV escape from the anti-viral response triggered by activating Fc��R.,經由抗體免疫作用後的登革病毒會結合上  Aantibody-opsonized(? explanation) DENV colligates(?explanation) leukocyte Ig-like B1受器(leukocyte Ig-like receptor-B1 ，(LILRB1) 以抑制ISG的表現．to inhibit Fc��R signaling for ISGs expression. LILRB1 (also known as也被稱為CD85j or Ig-like transcript-2)是一個 is a tyrosine-based inhibition motif-bearing receptor 受器表現在單核球、樹突狀細胞及T細胞及自然殺手細胞表面．LILRB1的自然生理功能是藉由結合主要組織相容性複合物(major histocompatibility complex class I ，MHC-I)活化負回饋機制 and, expresses on monocyte, dendritic cekk and as well as subsets of T cell and NK cel．ls.Lilbr1(? consistency) LILRB1 recruits召集 Src homology phosphatase-1 to dephosphate以去磷酸化 spleen tyrosine kinase (Syk), 此舉在STAT-1誘發ISGs表現這條訊息路徑上扮演著重要的角色．which plays an important role in STAT-1 signaling pathway to induce ISG expression [2]. 藉由結合Through colligatione with LILBR1, 經抗體免疫後的登革病毒可抑制由Fc-gamma受器誘發的ISGs的表現．此一機制使得抗體依賴增強效應的登革病毒感染得以成功．antibody-opsonized DENV will is able to inhibit Fc��R-activated early ISG expression. 因此，抑制登革病毒活化This mechanism is required for successful antibody-dependent DENV infection. Thus, inhibition of DENV activation of LILRB1可為設計疫苗或治療用藥的策略之一．could be a strategy for vaccine or therapeutic design.

References:

1. Halstead S.B., Orurke E. J.  (1988) Pathogenesis of dengue: Challenges to molecular biology. Science 239(4839):476–481 (1988).

2. Tassiulas I., Xiaoyu H., Hao H., Yogita K., Paul P., Yongmei H., Calliford A. L., Lionel B. I. et al. (2004) Amplification of IFN-alpha-induced STAT1 activation and inflammatory function bySyk and ITAM-containing adaptors. Nat Immunol 5(11):

1181–1189 (2004).