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An Assessment Of The Use Of Chimpanzees In Hepatitis C Research Past, Present And Future: 1. Validity Of The Chimpanzee Model, Jarrod Bailey
An Assessment Of The Use Of Chimpanzees In Hepatitis C Research Past, Present And Future: 1. Validity Of The Chimpanzee Model, Jarrod Bailey
Jarrod Bailey, PhD
The USA is the only significant user of chimpanzees in biomedical research in the world, since many countries have banned or limited the practice due to substantial ethical, economic and scientific concerns. Advocates of chimpanzee use cite hepatitis C research as a major reason for its necessity and continuation, in spite of supporting evidence that is scant and often anecdotal. This paper examines the scientific and ethical issues surrounding chimpanzee hepatitis C research, and concludes that claims of the necessity of chimpanzees in historical and future hepatitis C research are exaggerated and unjustifiable, respectively. The chimpanzee model has several major …
An Assessment Of The Use Of Chimpanzees In Hepatitis C Research Past, Present And Future: 2. Alternative Replacement Methods, Jarrod Bailey
An Assessment Of The Use Of Chimpanzees In Hepatitis C Research Past, Present And Future: 2. Alternative Replacement Methods, Jarrod Bailey
Jarrod Bailey, PhD
The use of chimpanzees in hepatitis C virus (HCV) research was examined in the report associated with this paper (1: Validity of the Chimpanzee Model), in which it was concluded that claims of past necessity of chimpanzee use were exaggerated, and that claims of current and future indispensability were unjustifiable. Furthermore, given the serious scientific and ethical issues surrounding chimpanzee experimentation, it was proposed that it must now be considered redundant — particularly in light of the demonstrable contribution of alternative methods to past and current scientific progress, and the future promise that these methods hold. This paper builds on …
Alcohol And Hcv: Implications For Liver Cancer, Gyongyi Szabo, Banishree Saha, Terence Bukong
Alcohol And Hcv: Implications For Liver Cancer, Gyongyi Szabo, Banishree Saha, Terence Bukong
Gyongyi Szabo
Liver cancers are one of the deadliest known malignancies which are increasingly becoming a major public health problem in both developed and developing countries. Overwhelming evidence suggests a strong role of infection with hepatitis B and C virus (HBV and HCV), alcohol abuse, as well as metabolic diseases such as obesity and diabetes either individually or synergistically to cause or exacerbate the development of liver cancers. Although numerous etiologic mechanisms for liver cancer development have been advanced and well characterized, the lack of definite curative treatments means that gaps in knowledge still exist in identifying key molecular mechanisms and pathways …
Interview With Celia Schiffer, Celia Schiffer
Interview With Celia Schiffer, Celia Schiffer
Celia A. Schiffer
Celia Schiffer, a Professor in Biochemistry and Molecular Pharmacology; a former Director of UMass Center for AIDS Research; and a Founder and Co-Director for the Institute for Drug Resistance (University of Massachusetts Medical School, MA, USA). Schiffer has an undergraduate degree in physics from the University of Chicago, with a PhD in biophysics from University of California, San Francisco (CA, USA). She was a postdoctoral associate first at the ETH in Zurich and then at Genentech in San Francisco. Schiffer has published more than 100 peer reviewed journal articles. Her laboratory primarily uses structural biology, biophysical and chemistry techniques to …
Human Ezrin-Moesin-Radixin Proteins Modulate Hepatitis C Virus Infection, Terence Bukong, Karen Kodys, Gyongyi Szabo
Human Ezrin-Moesin-Radixin Proteins Modulate Hepatitis C Virus Infection, Terence Bukong, Karen Kodys, Gyongyi Szabo
Gyongyi Szabo
Host cytoskeletal proteins of the ezrin-moesin-radixin (EMR) family have been shown to modulate single-stranded RNA virus infection through regulating stable microtubule formation. Antibody engagement of CD81, a key receptor for hepatitis C virus (HCV) entry, induces ezrin phosphorylation. Here we tested the role of EMR proteins in regulating HCV infection and explored potential therapeutic targets. We show that HCV E2 protein induces rapid ezrin phosphorylation and its cellular redistribution with F-actin by way of spleen tyrosine kinase (SYK). Therapeutically blocking the functional roles of SYK or F-actin reorganization significantly reduced Huh7.5 cell susceptibility to HCV J6/JFH-1 infection. Using gene regulation, …
Dendritic Cells In Hepatitis C Infection: Can They (Help) Win The Battle, Angela Dolganiuc, Gyongyi Szabo
Dendritic Cells In Hepatitis C Infection: Can They (Help) Win The Battle, Angela Dolganiuc, Gyongyi Szabo
Gyongyi Szabo
Infection with hepatitis C virus (HCV) is a public health problem; it establishes a chronic course in ~85% of infected patients and increases their risk for developing liver cirrhosis, hepatocellular carcinoma, and significant extrahepatic manifestations. The mechanisms of HCV persistence remain elusive and are largely related to inefficient clearance of the virus by the host immune system. Dendritic cells (DCs) are the most efficient inducers of immune responses; they are capable of triggering productive immunity and maintaining the state of tolerance to self- and non-self antigens. During the past decade, multiple research groups have focused on DCs, in hopes of …
Cd81/Cd9 Tetraspanins Aid Plasmacytoid Dendritic Cells In Recognition Of Hcv-Infected Cells And Induction Of Ifnalpha, Shuye Zhang, Karen Kodys, Gregory Babcock, Gyongyi Szabo
Cd81/Cd9 Tetraspanins Aid Plasmacytoid Dendritic Cells In Recognition Of Hcv-Infected Cells And Induction Of Ifnalpha, Shuye Zhang, Karen Kodys, Gregory Babcock, Gyongyi Szabo
Gyongyi Szabo
Recognition of hepatitis C virus (HCV)-infected hepatocyes and interferon (IFN) induction are critical in antiviral immune response. We hypothesized that cell-cell contact between plasmacytoid dendritic cells (pDCs) and HCV-infected cells was required for IFNalpha induction via involvement of cell surface molecules. Co-culture of human peripheral blood mononuclear cells (PBMCs) with genotype 1a full length HCV genomic replicon cells (FL) or genotype 2a JFH-1 virus infected hepatoma cells (JFH-1), not with uninfected hepatoma cells (Huh7.5), induced IFNalpha production. Depletion of pDCs from PBMCs attenuated IFNalpha release and purified pDCs produced high levels of IFNalpha after co-culture with FL replicons or JFH-1 …
Hepatitis C Core And Nonstructural 3 Proteins Trigger Toll-Like Receptor 2-Mediated Pathways And Inflammatory Activation, Angela Dolganiuc, Shilpa Oak, Karen Kodys, Douglas Golenbock, Robert Finberg, Evelyn Kurt-Jones, Gyongyi Szabo
Hepatitis C Core And Nonstructural 3 Proteins Trigger Toll-Like Receptor 2-Mediated Pathways And Inflammatory Activation, Angela Dolganiuc, Shilpa Oak, Karen Kodys, Douglas Golenbock, Robert Finberg, Evelyn Kurt-Jones, Gyongyi Szabo
Gyongyi Szabo
BACKGROUND AND AIMS: Recent evidence suggests that toll-like receptors (TLRs) recognize certain viruses. We reported that hepatitis C virus (HCV) core and nonstructural 3 (NS3) proteins activate inflammatory pathways in monocytes. The aim of this study was to investigate the role of TLRs in innate immune cell activation by core and NS3 proteins. METHODS: Human monocytes, human embryonic kidney cells transfected with TLR2, and peritoneal macrophages from TLR2, MyD88 knockout, and wild-type mice were studied to determine intracellular signaling and proinflammatory cytokine induction by HCV proteins. RESULTS: HCV core and NS3 proteins triggered inflammatory cell activation via the pattern recognition …
Inhibition Of Antigen-Presenting Cell Functions By Alcohol: Implications For Hepatitis C Virus Infection, Gyongyi Szabo, Angela Dolganiuc, Pranoti Mandrekar, Bernadette White
Inhibition Of Antigen-Presenting Cell Functions By Alcohol: Implications For Hepatitis C Virus Infection, Gyongyi Szabo, Angela Dolganiuc, Pranoti Mandrekar, Bernadette White
Gyongyi Szabo
The mechanisms of alcohol-induced immunosuppression include defects in innate and adaptive immune responses. Monocytes and dendritic cells (DCs) link innate and adaptive immune responses as they recognize viral antigens and induce antigen-specific T-cell activation. We investigated the effects of alcohol on antigen-presenting cell functions. Acute alcohol consumption by healthy volunteers (vodka, 2 ml/kg) resulted in significantly reduced antigen-presenting cell function of monocyte-derived DCs. Reduced allostimulatory capacity of DCs treated with alcohol in vitro correlated with decreased co-stimulatory molecule (B7.1 and B7.2) expression, as well as with reduced interleukin (IL)-12 and increased IL-10 concentrations, in mixed lymphocyte cultures. Dendritic cells recognize …
Hepatitis C Virus Ns5a Protein--A Master Regulator, Gyongyi Szabo
Hepatitis C Virus Ns5a Protein--A Master Regulator, Gyongyi Szabo
Gyongyi Szabo
No abstract provided.
T Cells With Regulatory Activity In Hepatitis C Virus Infection: What We Know And What We Don't, Angela Dolganiuc, Gyongyi Szabo
T Cells With Regulatory Activity In Hepatitis C Virus Infection: What We Know And What We Don't, Angela Dolganiuc, Gyongyi Szabo
Gyongyi Szabo
The mechanism behind the apparent lack of effective antiviral immune response in patients with chronic hepatitis C virus (HCV) infection is poorly understood. Although multiple levels of abnormalities have been identified in innate and adaptive immunity, it remains unclear if any of the subpopulations of T cells with regulatory capacity (Tregs) contribute to the induction and maintenance of HCV persistence. In this review, we summarize the current knowledge about Tregs as they relate to HCV infection.
Hepatitis C And Innate Immunity: Recent Advances, Gyongyi Szabo, Angela Dolganiuc
Hepatitis C And Innate Immunity: Recent Advances, Gyongyi Szabo, Angela Dolganiuc
Gyongyi Szabo
Eradication of hepatitis C virus (HCV) infection requires a complex and coordinated interplay between innate and adaptive immune responses that, when it fails, leads to chronic infection. In this review, the innate immune mechanisms by which HCV is sensed and by which HCV undermines host defense are discussed. The critical role of dendritic cells in antigen presentation and T-cell activation in addition to type I interferon production and interference of HCV with innate immune cell functions are reviewed. Finally, current and emerging therapeutic approaches targeting innate immune pathways are evaluated.
An Intervention To Prevent Symptoms Associated With Hepatitis C: A Pilot Study, Donna M. Zucker
An Intervention To Prevent Symptoms Associated With Hepatitis C: A Pilot Study, Donna M. Zucker
Donna M. Zucker
The objectives of this study were to (a) pilot test instruments measuring fatigue and quality of life (QOL); (b) pilot test an exercise intervention; and (c) estimate the effect size of this intervention relative to completion of combination therapy, fatigue, QOL, and walking distance in 20 patients with chronic hepatitis C about to begin interferon alpha and ribavirin treatment. Alpha reliabilities for both the Schwartz Cancer Fatigue Scale and Hepatitis Quality of Life Questionnaire were moderately high. Power analyses of all outcome measures indicated a small effect size and sample size estimate of 30–40 per group to achieve power of …
Peer Education For Hepatitis C Prevention, Donna M. Zucker
Peer Education For Hepatitis C Prevention, Donna M. Zucker
Donna M. Zucker
The purpose of this article is to describe a model of education about hepatitis C virus prevention tested in a county correctional facility. The Teach One Method and Relational Communication models inform this work. Using a one-group pretest–posttest prospective design our aims were to (1) convey education about prevention, protection, and safety; (2) provide this information through relationship-centered communication; (3) test the reliability and validity of the instruments; and (4) measure changes in behavior, knowledge, and relationship in the learner. A convenience sample of 25 men was recruited at a Massachusetts county jail. Subscale reliability was 0.78 and 0.79 for …