Zika NS1-induced ER remodeling is essential for viral replication.

Zika virus (ZIKV), a recently emerged member of the flavivirus family, forms replication compartments at the ER during its lifecycle. The proteins that are responsible for the biogenesis of replication compartments are not well defined. Here, we show that Zika nonstructural protein 1 (NS1)-induced ER remodeling is essential for viral replication.

Interferon down-regulation of miR-1225-3p as an antiviral mechanism through modulating Grb2-associated binding protein 3 expression.

Induction of interferons (IFNs) is a central event of antiviral innate immunity. As crucial posttranscriptional regulators, microRNAs (miRNAs) are important for IFN-mediated host defense. Although screening has indicated a substantial number of miRNAs to be differentially expressed after IFN stimulation, the detailed mechanisms of these miRNAs in the antiviral response are underexplored and of great significance.

Fusion expression of Occludin extracellular loops and an α-helical bundle: A new research model for tight junction.

Tight junctions (TJs) are the outermost structures of intercellular junctions and are highly specialized membrane domains involved in many important cellular processes. However, most TJ proteins are four-time transmembrane proteins and are difficult to express in their correct soluble form, which limits their functional study and therapeutic application. Human occludin (OCLN) is a major component of TJs and an essential co-receptor for hepatitis C virus (HCV) cell entry.

Identification of a novel human long non-coding RNA that regulates hepatic lipid metabolism by inhibiting SREBP-1c.

Sterol regulatory element binding proteins (SREBPs) are master regulators of hepatic lipid homeostasis. Aberrant expression of SREBPs frequently leads to lipid metabolism dysregulation. Long non-coding RNAs (lncRNAs) have been identified with diverse biological functions, but the effects of lncRNAs on lipid metabolism are rarely reported.

Identification of a Potent and Broad-Spectrum Hepatitis C Virus Fusion Inhibitory Peptide from the E2 Stem Domain.

Hepatitis C virus (HCV) envelope proteins E1 and E2 play an essential role in virus entry. However, the fusion mechanisms of HCV remain largely unclear, hampering the development of efficient fusion inhibitors. Here, we developed two cell-based membrane fusion models that allow for screening a peptide library covering the full-length E1 and E2 amino acid sequences.

AP1S3 is required for hepatitis C virus infection by stabilizing E2 protein.

Hepatitis C virus (HCV) infects 130 million people worldwide and is a leading cause of liver cirrhosis, end-stage liver disease and hepatocellular carcinoma. The interactions between viral elements and host factors play critical role on HCV invade, replication and release. Here, we identified adaptor protein complex 1 sigma 3 subunit (AP1S3) as a dependency factor for the efficient HCV infection in hepatoma cells.

Association of serum level of growth differentiation factor 15 with liver cirrhosis and hepatocellular carcinoma.

Hepatocellular carcinoma (HCC) and liver cirrhosis are associated with high mortality worldwide. Currently, alpha-fetoprotein (AFP) is used as a standard serum marker for the detection of HCC, but its sensitivity and specificity are unsatisfactory, and optimal diagnostic markers for cirrhosis are lacking. We previously reported that growth differentiation factor 15 (GDF15) was significantly induced in HCV-infected hepatocytes.

A novel small-molecule inhibitor of hepatitis C virus replication acts by suppressing signal transducer and activator of transcription 3.

Objectives: Hepatitis C virus (HCV) infects hepatocytes and causes liver damage. The aim of this study was to identify new classes of host-targeting anti-HCV compounds that may provide novel approaches for antiviral treatment regimens.

Methods: Cell culture-derived HCV (HCVcc), replicons and pseudoparticles were used in combination with high-throughput screening, reporter gene assays and cytotoxicity and signalling pathway analyses.

Entry properties and entry inhibitors of a human H7N9 influenza virus.

The recently identified human infections with a novel avian influenza H7N9 virus in China raise important questions regarding possible risk to humans. However, the entry properties and tropism of this H7N9 virus were poorly understood. Moreover, neuraminidase inhibitor resistant H7N9 isolates were recently observed in two patients and correlated with poor clinical outcomes.

High-throughput profiling of alpha interferon- and interleukin-28B-regulated microRNAs and identification of let-7s with anti-hepatitis C virus activity by targeting IGF2BP1.

Hepatitis C virus (HCV) infection is a major cause of severe liver disease. Interferon (IFN)/ribavirin treatment remains the standard therapeutic regimen for HCV infection in most countries. IFN-stimulated genes are believed to contribute to antiviral effects.

Albumin fusion of interleukin-28B: production and characterization of its biological activities and protein stability.

The cytokine interleukin-28B (IL-28B) has potential antiviral properties and regulatory roles in adaptive cellular immunity. A genome-wide association study identified a single nucleotide polymorphism near the IL-28B gene that strongly predicts response to hepatitis C treatment with interferon and ribavirin. In this study, we produced human serum albumin (HSA) fused to interleukin-28B (HSA-IL28B) in an attempt to determine the effects of albumin fusion on anti-Hepatitis C virus (HCV) activity and protein stability.

Screening and rational design of hepatitis C virus entry inhibitory peptides derived from GB virus A NS5A.

Chronic infection by hepatitis C virus (HCV) is a cause of the global burden of liver diseases. HCV entry into hepatocytes is a complicated and multistep process that represents a promising target for antiviral intervention. The recently reported amphipathic α-helical virucidal peptide (C5A) from the HCV NS5A protein suggests a new category of antiviral drug candidates.

A human claudin-1-derived peptide inhibits hepatitis C virus entry.

Unlabelled: Hepatitis C virus (HCV) entry is a complicated process that requires multiple host factors, such as CD81, scavenger receptor BI, claudin-1 (CLDN1), and occludin. The interaction of virus and cellular entry factors represents a promising target for novel anti-HCV drug development. In this study, we sought to identify peptide inhibitors for HCV entry by screening a library of overlapping peptides covering the four above-mentioned entry factors.

Recombinant human interleukin 28B: anti-HCV potency, receptor usage and restricted cell-type responsiveness.

Objectives: Interleukin 28B (IL28B) genetic variation has been recently reported as a potent predictor of hepatitis C virus (HCV) response to interferon (IFN) therapy. The aim of this study was to produce recombinant human IL28B (rhIL28B) in yeast and explore the action mechanisms of rhIL28B as a novel anti-HCV agent.

Methods: A simple and efficient protocol for producing rhIL28B in the methylotrophic yeast Pichia pastoris was developed.

LFR, which encodes a novel nuclear-localized Armadillo-repeat protein, affects multiple developmental processes in the aerial organs in Arabidopsis.

The Armadillo (ARM)-repeat domain is a 42-amino acid protein-protein interaction motif present in many eukaryotic proteins. ARM-repeat proteins function in many cellular processes, including cytoskeletal regulation, nucleo-cytoplasmic trafficking, and transcriptional regulation. More than 100 genes encoding ARM-repeat proteins are predicted to exist in the Arabidopsis thaliana genome; however, most of them have unknown biological functions.