Identification of a functional ITAM-like sequence within G1 cytoplasmic tail of Hantaan virus / 病毒学报

The G1 cytoplasmic tail of Hantaan virus (HTNV) harbors a highly conserved region, which is homologous to immunoreceptor tyrosine-based activation motifs (ITAM) and is termed the ITAM-like sequence. To demonstrate the potential signal-transducing activity of G1 ITAM-like sequence resembling the canonical ITAM within immune and endothelial cells, a series of experiments were performed to define its interaction with cellular kinases. The synthesized G1 ITAM-like peptide was shown to coprecipitate with cellular phosphoprotein complexes by an immune-complex kinase assay. Mutational analyses showed that this ITAM-like sequence was a substrate for the Src family kinase Fyn, and two conserved tyrosine residues were required for coprecipitating Lyn, Syk, and ZAP-70 kinases. These findings demonstrated that HTNV envelope glycoprotein G1 contains a functional ITAM-like sequence in its cytoplasmic tail, which can bind critical cellular kinases that regulate immune and endothelial cell functions.

DC-SIGN: binding receptors for hepatitis C virus / 中华医学杂志(英文版)

<p><b>OBJECTIVE</b>To review the recent developments in and research into binding receptors of hepatitis C virus (HCV) and especially the role of dendritic cell-specific adhesion receptor (DC-SIGN) in HCV.</p><p><b>DATA SOURCES</b>Both Chinese- and English-language literature was searched using MEDLINE (2000 - 2003) and the databank of Chinese-language literature (2000 - 2003).</p><p><b>STUDY SELECTION</b>Relevant articles on DC-SIGN and HCV binding receptors in recent domestic and foreign literature were selected.</p><p><b>DATA EXTRACTION</b>Data were mainly extracted from 40 articles which are listed in the references section of this review.</p><p><b>RESULTS</b>DC-SIGN, a dendritic cell-specific adhesion receptor and a type II transmembrane mannose-binding C-type lectin, is very important in the function of dendritic cells (DC), both in mediating naïve T cell interactions through ICAM-3 and as a rolling receptor that mediates the DC-specific ICAM-2-dependent migration processes. It can be used by HCV and other viral and bacterial pathogens including human immunodeficiency virus (HIV), Ebola virus, CMV and Mycobacterium tuberculosis to facilitate infection. Both DC-SIGN and DC-SIGNR can act either in cis, by concentrating virus on target cells, or in trans, by transmission of bound virus to a target cell expressing appropriate entry receptors. Recent report showed that DC-SIGN not only plays a role in entry into DC, HCV E2 interaction with DC-SIGN might also be detrimental to the interaction of DC with T cells during antigen presentation.</p><p><b>CONCLUSIONS</b>DC-SIGNs are high-affinity binding receptors for HCV. The clinical strategies that target DC-SIGN may be successful in restricting HCV dissemination and pathogenesis as well as directing the migration of DCs to manipulate appropriate immune responses in autoimmunity and tumorigenic situations.</p>