Leukocyte immunoglobulin-like receptor B1 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:

   Dengue virus (DENV) is a single-stranded ssRNA virus, belonging to Flaviviridae, transmitted by Aedes spp. mosquitoes and causes 390 million infections annually. Secondary infection with hetero serotype of DENV will increases virus entry into Fc-gamma receptor (FcgR) bearing cell, monocyte, macrophagy and dendricted cells, and this phenomenon is known as antibody-dependent enhancement (ADE) of DENV infection [1]. Severe dengue disease, dengue hemorrhagic fever (DHF) and dengue shock syndrome (DSS) were are closely related to ADE because of the resultantwhich results in greater increased viral burden to increase systemic inflammation. Intriguingly, in the previous study, this enhancement of DENV infection will activates early FcgR earlyanti-virus signals by through inducing the type-I IFN-stimulated genes (ISGs).

   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 FcgR.,  Aantibody-opsonized(? explanation)immunized  DENV bindscolligates(? explanation) leukocyte Ig-like receptor-B1 (LILRB1) to inhibit FcgR signaling for ISGs expression. LILRB1 (also known as CD85j or Ig-like transcript-2) is a tyrosine-based inhibition motif-bearing receptor and, expresses on monocyte, dendritic cekk cell and as well as subsets of T cell and NK cells. The natural function of LILRB1 is to activate negative feedback mechanisms upon binding to major histocompatibility complex class I (MHC-I) molecule. . Lilbr1(? consistency) LILRB1 recruits Src homology phosphatase-1 todephosphate spleen tyrosine kinase (Syk), which plays an important role in STAT-1 signaling pathway to induce ISG expression [2]. Through colligationbindinge with LILBR1, antibody-immunized opsonized DENV will is able to inhibit FcgR-activated early ISG expression. This mechanism is required for successful antibody-dependent DENV infection. Thus, inhibition of DENV activation of LILRB1 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).