Life Sciences Commons^™

An Assessment Of The Use Of Chimpanzees In Hepatitis C Research Past, Present And Future: 2. Alternative Replacement Methods, Jarrod Bailey

Experimentation Collection

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 …

An Assessment Of The Use Of Chimpanzees In Hepatitis C Research Past, Present And Future: 1. Validity Of The Chimpanzee Model, Jarrod Bailey

Experimentation Collection

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 …

Hepatitis C Virus Core-Derived Peptides Inhibit Genotype 1b Viral Genome Replication Via Interaction With Ddx3x, Chaomin Sun, Cara T. Pager, Guangxiang Luo, Peter Sarnow, Jamie H. D. Cate

Microbiology, Immunology, and Molecular Genetics Faculty Publications

The protein DDX3X is a DEAD-box RNA helicase that is essential for the hepatitis C virus (HCV) life cycle. The HCV core protein has been shown to bind to DDX3X both in vitro and in vivo. However, the specific interactions between these two proteins and the functional importance of these interactions for the HCV viral life cycle remain unclear. We show that amino acids 16-36 near the N-terminus of the HCV core protein interact specifically with DDX3X both in vitro and in vivo. Replication of HCV replicon NNeo/C-5B RNA (genotype 1b) is significantly suppressed in HuH-7-derived cells expressing green fluorescent …

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

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

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

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

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.

Prognostic Value Of Ishak Fibrosis Stage: Findings From The Halt-C Trial, Herbert L. Bonkovsky

UCHC Articles - Research

Background and Aims

Studies of the prognostic value of Ishak fibrosis stage are lacking. We utilized multi-year follow-up of the Hepatitis C Antiviral Long Term Treatment Against Cirrhosis (HALT-C) Trial to determine whether individual Ishak fibrosis stages predicted clinical outcomes in patients with chronic hepatitis C.

Methods

Baseline liver biopsies from 1,050 patients with compensated chronic hepatitis C who had failed combination peginterferon and ribavirin were reviewed by a panel of expert hepatopathologists. Fibrosis was staged with the Ishak scale (ranging from 0=no fibrosis to 6=cirrhosis). Biopsy fragmentation and length as well as number of portal tracts were recorded. We …

An Intervention To Prevent Symptoms Associated With Hepatitis C: A Pilot Study, Donna M. Zucker

Elaine Marieb College of Nursing Faculty Publication Series

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 …

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 …