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Author (up) Chen, X.; Qian, Y.; Yan, F.; Tu, J.; Yang, X.; Xing, Y.; Chen, Z. file  url
openurl 
  Title 5'-triphosphate-siRNA activates RIG-I-dependent type I interferon production and enhances inhibition of hepatitis B virus replication in HepG2.2.15 cells Type Journal Article
  Year 2013 Publication European Journal of Pharmacology Abbreviated Journal Eur J Pharmacol  
  Volume 721 Issue 1-3 Pages 86-95  
  Keywords Base Sequence; DEAD-box RNA Helicases/*metabolism; DNA Replication/genetics; Hep G2 Cells; Hepatitis B Antigens/genetics/metabolism; Hepatitis B virus/*genetics/*physiology; Humans; Immunity, Innate; Interferon Type I/*biosynthesis/genetics; Polyphosphates/*chemistry; RNA Interference; RNA, Messenger/genetics; RNA, Small Interfering/chemistry/*genetics; Transcription, Genetic/genetics; Virus Replication/*genetics; 3-(4,5)-dimethylthiahiazol-2-y1)-2,5-diphenytetrazolium bromide; 3p-siRNA; 5â²-Triphosphated siRNA; 5â²-triphosphated siRNA; BF-siRNA; Ciap; Elisa; Hbv; HBV e antigen; HBV s antigen; HBeAg; HBsAg; Hcc; HepG2.2.15 cells; Hepatitis B virus; Ifn; Ifnî±/β; Mtt; NC-siRNA; Od; Prr; Rig-I; RNA interference; RNAi; Rt-Pcr; Tlr; bifunctional siRNA; calf intestine alkaline phosphatase; double strand DNA; double strand RNA; dsDNA; dsRNA; enzyme-linked immunosorbent assay; hepatitis B virus; hepatocellular carcinoma; interferon; negative control siRNA; optical density; pathogen-recognition receptor; retinoic acid-inducible gene I; reverse transcription PCR; siRNA; single strand RNA; small interfering RNA; ssRNA; toll-like receptor  
  Abstract Hepatitis B virus (HBV) infection often results in acute or chronic viral hepatitis and other liver diseases including cirrhosis and hepatocellular carcinoma. Current therapies for HBV usually have severe side effects and can cause development of drug-resistant mutants. An alternative and safe immunotherapeutic approach for HBV infection is urgently needed for effective anti-HBV therapy. In this study, we propose a new strategy for anti-HBV therapy that activates type-I interferon (IFN) antiviral innate immunity through stimulating pattern-recognition receptors with RNA interference (RNAi) using a 5'-end triphosphate-modified small interfering RNA (3p-siRNA). We designed and generated a 3p-siRNA targeting overlapping region of S gene and P gene of the HBV genome at the 5'-end of pregenomic HBV RNA. Our results demonstrated that 3p-siRNA induced a RIG-I-dependent antiviral type-I IFN response when transfected into HepG2.2.15 cells that support HBV replication. The 3p-siRNA significantly inhibited HBsAg and HBeAg secretion from HepG2.2.15 cells in a RIG-I-dependent manner, and the antiviral effect of 3p-siRNA was superior to that of siRNA. Furthermore, 3p-siRNA had more pronounced inhibition effects on the replication of HBV DNA and the transcription of mRNA than that of siRNA. Finally, 3p-siRNA displayed antiviral activity with long-term suppression of HBV replication. In conclusion, our findings suggest that 3p-siRNA could act as a powerful bifunctional antiviral molecule with potential for developing a promising therapeutic against chronic HBV infection.  
  Call Number Serial 1013  
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Author (up) Dhib-Jalbut, S.; Marks, S. file  url
openurl 
  Title Interferon-beta mechanisms of action in multiple sclerosis Type Journal Article
  Year 2010 Publication Neurology Abbreviated Journal Neurology  
  Volume 74 Suppl 1 Issue Pages S17-24  
  Keywords Animals; Antigen-Presenting Cells/*immunology; Cytokines/immunology; Humans; Immunity, Innate/*immunology; Immunologic Factors/*immunology; Interferon-beta/*immunology; *Models, Immunological; Multiple Sclerosis/*immunology; T-Lymphocytes/*immunology  
  Abstract ABSTRACT Multiple sclerosis (MS) is a chronic autoimmune disease of the CNS characterized by inflammation, demyelination, and axonal injury. These pathologic effects are manifested in clinical symptoms of relapse and disability. Various disease-modifying therapies have been developed in recent years to modulate the body's immune response. Among the most widely used are the beta interferons (IFNbeta). All produce comparable biological effects and are approved for the treatment of relapsing-remitting MS (RRMS). Although the precise mechanisms through which IFNbeta achieves its antiinflammatory and immunomodulatory effects remain uncertain, several modes of action have been proposed, including inhibition of T-cell activation and proliferation; apoptosis of autoreactive T cells; induction of regulatory T cells; inhibition of leukocyte migration across the blood-brain barrier; cytokine modulation; and potential antiviral activity. Endogenously produced IFNbeta in the injured brain is also now believed to contribute to mediation of antiinflammatory and regenerative effects. All these mechanisms are believed to underlie the therapeutic effect of IFNbeta in the treatment of RRMS.  
  Call Number Serial 1015  
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Author (up) IFNB Multiple Sclerosis Study Group file  url
openurl 
  Title Interferon beta-1b is effective in relapsing-remitting multiple sclerosis. I. Clinical results of a multicenter, randomized, double-blind, placebo-controlled trial. The IFNB Multiple Sclerosis Study Group Type
  Year 1993 Publication Neurology Abbreviated Journal Neurology  
  Volume 43 Issue 4 Pages 655-661  
  Keywords Adult; Double-Blind Method; Enzyme-Linked Immunosorbent Assay; Female; Humans; Interferon-beta/adverse effects/*therapeutic use; Lymphopenia/etiology; Magnetic Resonance Imaging; Male; Middle Aged; Multiple Sclerosis/diagnosis/*therapy; Neurologic Examination; Recurrence; Treatment Outcome  
  Abstract We report a multicenter, randomized, double-blind, placebo-controlled trial of interferon beta-1b (IFNB) in 372 ambulatory patients with relapsing-remitting multiple sclerosis (MS). Entry criteria included an Expanded Disability Status Scale (EDSS) score of 0 to 5.5 and at least two exacerbations in the previous 2 years. One-third of the patients received placebo, one-third 1.6 million international units (MIU) of IFNB, and one-third 8 MIU of IFNB, self-administered by subcutaneous injections every other day. The primary end points were differences in exacerbation rates and proportion of patients remaining exacerbation-free. The annual exacerbation rate for patients receiving placebo was 1.27; for 1.6 MIU IFNB, 1.17; and for 8 MIU IFNB, 0.84 after 2 years. Exacerbation rates were significantly lower in both treatment groups compared with the placebo group (8 MIU versus placebo, p = 0.0001; 1.6 MIU versus placebo, p = 0.0101; and 8 MIU versus 1.6 MIU, p = 0.0086), suggesting a dosage effect. The reduction in exacerbation severity in the 8 MIU group was attributable to a twofold reduction in the frequency of moderate and severe attacks. More patients in the 8 MIU group (n = 36) were exacerbation-free at 2 years compared with the placebo group (n = 18; p = 0.007). EDSS scores changed little from baseline in both the placebo and treatment arms. Accordingly, a significant change in disability could not be discerned in this trial. Finally, in serial MRIs, MS activity was significantly less in the high-dose IFNB group.  
  Call Number Serial 1003  
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Author (up) Petzke, M.; Schwartz, I. file  url
openurl 
  Title Borrelia burgdorferi Pathogenesis and the Immune Response Type Journal Article
  Year 2015 Publication Clinics in Laboratory Medicine Abbreviated Journal Clin Lab Med  
  Volume 35 Issue 4 Pages 745-764  
  Keywords Animals; Antigens, Bacterial/analysis; Borrelia burgdorferi/genetics/*immunology/*pathogenicity; Humans; Immune Evasion; Immunity, Innate; Integrins/metabolism; Adhesins; Genotypic variation; Immune evasion; Lyme disease; Type I interferon  
  Abstract Borrelia burgdorferi is the tick-borne etiologic agent of Lyme disease. The spirochete must negotiate numerous barriers in order to establish a disseminated infection in a mammalian host. These barriers include migration from the feeding tick midgut to the salivary glands, deposition in skin, manipulation or evasion of the localized host immune response, adhesion to and extravasation through an endothelial barrier, hematogenous dissemination, and establishment of infection in distal tissue sites. Borrelia burgdorferi proteins that mediate many of these processes and the nature of the host response to infection are described.  
  Call Number Serial 1746  
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Author (up) Zhang, S.-Y.; Jouanguy, E.; Ugolini, S.; Smahi, A.; Elain, G.; Romero, P.; Segal, D.; Sancho-Shimizu, V.; Lorenzo, L.; Puel, A.; Picard, C.; Chapgier, A.; Plancoulaine, S.; Titeux, M.; Cognet, C.; von Bernuth, H.; Ku, C.-L.; Casrouge, A.; Zhang, X.-X.; Barreiro, L.; Leonard, J.; Hamilton, C.; Lebon, P.; Heron, B.; Vallee, L.; Quintana-Murci, L.; Hovnanian, A.; Rozenberg, F.; Vivier, E.; Geissmann, F.; Tardieu, M.; Abel, L.; Casanova, J.-L. file  url
openurl 
  Title TLR3 deficiency in patients with herpes simplex encephalitis Type Journal Article
  Year 2007 Publication Science (New York, N.Y.) Abbreviated Journal Science  
  Volume 317 Issue 5844 Pages 1522-1527  
  Keywords Alleles; CD8-Positive T-Lymphocytes/immunology; Cell Line; Child, Preschool; Dendritic Cells/immunology; Encephalitis, Herpes Simplex/*genetics/*immunology; Female; Fibroblasts/immunology/metabolism/virology; Genes, Dominant; *Herpesvirus 1, Human/physiology; Heterozygote; Humans; Immunity, Innate; Infant; Interferons/biosynthesis; Keratinocytes/immunology; Killer Cells, Natural/immunology; Leukocytes, Mononuclear/immunology; Mutation; Poly I-C/pharmacology; Toll-Like Receptor 3/chemistry/*deficiency/*genetics/physiology  
  Abstract Some Toll and Toll-like receptors (TLRs) provide immunity to experimental infections in animal models, but their contribution to host defense in natural ecosystems is unknown. We report a dominant-negative TLR3 allele in otherwise healthy children with herpes simplex virus 1 (HSV-1) encephalitis. TLR3 is expressed in the central nervous system (CNS), where it is required to control HSV-1, which spreads from the epithelium to the CNS via cranial nerves. TLR3 is also expressed in epithelial and dendritic cells, which apparently use TLR3-independent pathways to prevent further dissemination of HSV-1 and to provide resistance to other pathogens in TLR3-deficient patients. Human TLR3 appears to be redundant in host defense to most microbes but is vital for natural immunity to HSV-1 in the CNS, which suggests that neurotropic viruses have contributed to the evolutionary maintenance of TLR3.  
  Call Number Serial 1730  
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