Hepatic expression of MxA and OAS1 in an ex vivo liver slice assay independently predicts treatment outcomes in chronic hepatitis C

Abstract

Antiviral effect of interferon is mediated by the expression of interferon-stimulated genes (ISGs). However, because of the difficulty in obtaining paired liver biopsies before and after interferon treatment, the key ISGs expressed in human hepatocytes and responsible for interferon-based antiviral activities in chronic hepatitis C remain illusive. Prior to a standard course of peginterferon plus ribavirin therapy, 104 patients underwent a liver biopsy. A small piece of the liver biopsy sample from each patient was submitted for ex vivo tissue culture in the presence or absence of interferon. Hepatic expression of 8 ISGs was detected by RT-PCR. The ISG expression patterns and clinicopathological variables were correlated with subsequent treatment outcomes. Multivariate logistic regression analysis showed that hepatic MxA expression (P = 0.008) and leucocyte count (P = 0.040) independently predicted the end of therapeutic virological response, while hepatic OAS1 expression (P = 0.003), genotype 1 (P = 0.002), HCV-RNA level (P = 0.007), AST/ALT ratio (P = 0.004) and leucocyte count (P = 0.034) independently predicted the sustained virological response. Immunohistochemistry analysis showed that interferon-induced OAS1 expression localized to the hepatocytes. In conclusion, hepatic MxA and OAS1 expression predicted, respectively, the end of therapeutic and sustained virological responses in interferon-based treatment of chronic hepatitis C.

Hyaluronic Acid–Gold Nanoparticle/Interferon α Complex for Targeted Treatment of Hepatitis C Virus Infection

“…OAS1 is expressed by IFNα stimulation and is one of the key components for the innate immune responses to HCV infection . OAS1 initiates the synthesis of 2′,5′-oligoadenylate, which activates the RNase L-associated pathway leading to the cleavage of viral and cellular RNAs .…”

“…After confirmation of in vitro antiproliferation activity and serum stability in Daudi cells, target-specific systemic delivery of HA–AuNP/IFNα complex was carried out for the treatment of chronic HCV infection. In vivo antiviral activity of HA–AuNP/IFNα complex was assessed by measuring the expression levels of OAS1, which is induced by IFNα and participates in innate immune responses to viral infection in the liver . The target-specific delivery system of HA–AuNP/IFNα complex was discussed for further clinical applications for the treatment of various liver diseases.…”

Fibrogenesis Genes and Susceptibility to Coronary Atherosclerosis

“…Белок 2'-5'-олигоаденилатсинтетаза 1-го типа, кодируемый геном OAS1, является протеином, индуцируемым интерфероном, оказывающим выраженное иммуномодулирующее действие на макрофаги, NK-клетки, Т-и В-лимфоциты. Полиморфные варианты гена ассоциированы с восприимчивостью к некоторым инфекционным, аутоиммунным заболеваниям, тяжестью течения ХВГС, прогрессией фиброза печени и ответом на интерферонотерапию [50][51][52]. В доступной научной литературе мы не обнаружили исследований ассоциаций SNP-маркеров гена OAS1 с ССЗ, тогда как в настоящем исследовании выявлен протективный эффект генотипа GG варианта rs1131454 гена OAS1, обусловливающего двукратное снижение риска развития ИМ у больных атеросклерозом.…”

Efficacy of IFN-λ1 to Protect Human Airway Epithelial Cells against Human Rhinovirus 1B Infection

“…Although type-I and type-III IFNs act through different receptors, both types of IFNs activate similar intracellular signaling pathways and because of this, they largely have similar biological activities. Both of them up-regulate the expression of ISGs, which are presumably responsible to provide antiviral resistance to the cells [35] , [36] . However, not all types of cells respond to type-III IFNs, which is due to the fact that expression of receptors for type-III IFNs is limited to a few types of cells.…”