Isolation and characterization of interferon lambda-resistant hepatitis C virus replicon cell lines

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• 作者：Jacques Friborg ; Baiqing Lin ; Chaoqun Chen ; Fiona McPhee
• 关键词：Interferon ; Lambda ; HCV ; Resistance
• 刊名：Virology
• 出版年：2013
• 出版时间：September, 2013
• 年：2013
• 卷：444
• 期：1-2
• 页码：384-393
• 全文大小：2707 K

文摘

Pegylated interferon lambda-1a (Lambda) is currently in clinical development for the treatment of chronic hepatitis C virus (HCV) infection. To gain insight into the potential mechanisms of non-responsiveness that may occur in patients treated with Lambda, HCV subgenomic replicon cell-lines with impaired susceptibility to the unpegylated recombinant (r) form of interferon (IFN) lambda-1 (rIFN¦Ë) were isolated and characterized. The selected replicon cell populations showed a defect in the activation of the IFN-dependent JAK-STAT signaling pathway. Reduced phosphorylation of STAT proteins and lower expression levels of the cellular janus kinases Jak1 and Tyk2 were observed in these cell populations, which may account for the impaired JAK-STAT signaling and reduced antiviral responses to rIFN¦Ë. Overall, this in vitro study provides molecular insights into the possible mechanism of viral evasion to rIFN¦Ë in the HCV replicon cell system.