Zika virus infection triggers lipophagy by stimulating the AMPK-ULK1 signaling in human hepatoma cells.

Zika virus (ZIKV) is a globally transmitted mosquito-borne pathogen, and no effective treatment or vaccine is available yet. Lipophagy, a selective autophagy targeting lipid droplets (LDs), is an emerging subject in cellular lipid metabolism and energy homeostasis. However, the regulatory mechanism of lipid metabolism and the role of lipophagy in Zika virus infection remain largely unknown.

Lipid Droplets and Their Participation in Zika Virus Infection.

Lipid droplets (LDs) are highly conserved and dynamic intracellular organelles. Their functions are not limited to serving as neutral lipid reservoirs; they also participate in non-energy storage functions, such as cell lipid metabolism, protection from cell stresses, maintaining protein homeostasis, and regulating nuclear function. During a Zika virus (ZIKV) infection, the viruses hijack the LDs to provide energy and lipid sources for viral replication.

Entry Inhibitors of Hepatitis C Virus.

Hepatitis C virus (HCV) infection affects approximately 1% of the world's population and is a major cause of chronic liver diseases. Although antiviral therapy consisting of direct-acting antivirals (DAAs) can cure the majority of HCV patients, it is still limited by viral resistances, drug-drug interactions, and high costs. Moreover, the role of DAAs in the prevention of occurrences of graft reinfection in HCV patients who receive liver transplantations is still under comprehensive clinical investigation, bringing the risk of recipient reinfection.

PTEN Lipid Phosphatase Activity Enhances Dengue Virus Production through Akt/FoxO1/Maf1 Signaling.

Dengue virus (DENV) is an arthropod-borne viral pathogen and a global health burden. Knowledge of the DENV-host interactions that mediate virus pathogenicity remains limited. Host lipid metabolism is hijacked by DENV for virus replication in which lipid droplets (LDs) play a key role during the virus lifecycle.

Retinoic acid induced 16 deficiency exacerbates high-fat diet-induced steatohepatitis in mice.

Non-alcoholic fatty liver disease (NAFLD) associated with obesity may progress to non-alcoholic steatohepatitis, cirrhosis and hepatocellular carcinoma (HCC). Retinoic acid induced 16 (RAI16) plays an important role in cell apoptosis and is also a potential marker for HCC. Here we aimed to test the effect of RAI16 deficiency on liver pathology in high-fat diet (HFD) fed mice.

Identification of retinoid acid induced 16 as a novel androgen receptor target in prostate cancer cells.

Background: Retinoid acid induced 16 (RAI16) was reported to enhance tumorigenesis in hepatocellular carcinoma (HCC). The androgen receptor (AR) is a nuclear hormone receptor that functions as a critical oncogene in several cancer progressions. However, whether RAI16 is a candidate AR target gene that may involve in prostate cancer progression was unclear.

Retinoid acid induced 16 deficiency aggravates colitis and colitis-associated tumorigenesis in mice.

Inflammatory bowel disease (IBD) and colitis-associated colorectal cancer (CAC) is a serious health issue, but etiopathological factors remain unclear. Although some studies reported the roles of Retinoid acid induced 16 (RAI16) in the tumorigenesis of hepatocellular carcinoma and PKA signaling, the roles of RAI16 in IBD and CRC are undressed. RAI16 mice were generated and the roles of RAI16 were addressed in dextran sodium sulfate (DSS) or azoxymethane (AOM)-DSS induced IBD or CAC mouse models, respectively.

Endophilin-A2-mediated endocytic pathway is critical for enterovirus 71 entry into caco-2 cells.

Enterovirus 71 (EV71) is typically transmitted by the oral-faecal route and initiates infection upon crossing the intestinal mucosa. Our limited understanding of the mechanisms by which it crosses the intestinal mucosa has hampered the development of effective therapeutic options. Here, using an RNA interference screen combined with chemical inhibitors or the overexpression of dominant negative proteins, we found that EV71 entry into Caco-2 cells, a polarized human intestinal epithelial cell line, does not involve clathrin- and caveolae-dependent endocytic pathways or macropinocytosis but requires GTP-binding protein dynamin 2 and cytoskeleton remodelling.

EDIL3 depletion suppress epithelial-mesenchymal transition of lens epithelial cells transforming growth factor β pathway.

Aim: To study the effect of discoidin I-like domaincontaining protein 3 (EDIL3) depletion on the proliferation and epithelial-mesenchymal transition (EMT) in human lens epithelial cells (LECs).

Methods: RNA interference was used to inhibit the expression of EDIL3 in human LECs . The morphology of cells was observed using an inverted microscope.

RIP3 deficiency ameliorates inflammatory response in mice infected with influenza H7N9 virus infection.

Influenza H7N9 virus infection causes an acute, highly contagious respiratory illness that triggers cell death of infected cells and airway epithelial destruction. RIP3 is a key regulator of cell death responses to a growing number of viral and microbial agents. This study aimed to investigate the role of RIP3 in inflammation of influenza H7N9 virus infection.

RIP3 deficiency exacerbates inflammation in dextran sodium sulfate-induced ulcerative colitis mice model.

Ulcerative colitis (UC) is a chronic intestinal inflammatory disease. The receptor-interacting protein kinase 3 (RIP3) was reported to be involved in many inflammatory disease. However, the mechanism of RIP3 in the pathogenesis of UC is still unclear.

Inhibition of STAT Pathway Impairs Anti-Hepatitis C Virus Effect of Interferon Alpha.

Background/aims: Signal transducer and activator of transcription (STAT) pathway plays an important role in antiviral efficacy of interferon alpha (IFN-α). IFN-α is the main therapeutic against hepatitis C virus (HCV) infection. We explored effects of IFN-α on HCV replication and antiviral gene expression by targeting STAT.

A Schisandra-Derived Compound Schizandronic Acid Inhibits Entry of Pan-HCV Genotypes into Human Hepatocytes.

Despite recent progress in the development of hepatitis C virus (HCV) inhibitors, cost-effective antiviral drugs, especially among the patients receiving liver transplantations, are still awaited. Schisandra is a traditional medicinal herb used to treat a range of liver disorders including hepatitis for thousands of years in China. To isolate the bioactive compounds of schisandra for the treatment of HCV infection, we screened a schisandra-extracts library and identified a tetracyclic triterpenoid, schizandronic acid (SZA), as a novel HCV entry inhibitor.

Interferon alpha antagonizes STAT3 and SOCS3 signaling triggered by hepatitis C virus.

We aimed to investigate regulation of signal transducer and activator of transcription 3 (STAT3) and suppressor of cytokine signaling 3 (SOCS3) by interferon alpha (IFN-α) and to analyze the relationship between STAT3 and SOCS3 during hepatitis C virus (HCV) infection. Changes in STAT3 and SOCS3 were analyzed at both mRNA and protein levels in human hepatoma cells infected with HCV (J6/JFH1). At 72h of HCV infection, STAT3 expression was decreased with sustained phosphorylation, and IFN-α increased such decrease and phosphorylation.

Trachelogenin, a novel inhibitor of hepatitis C virus entry through CD81.

Although much progress has been made in antiviral agents against hepatitis C virus (HCV) in recent years, novel HCV inhibitors with improved efficacy, optimized treatment duration and more affordable prices are still urgently needed. Here, we report the identification of a natural plant-derived lignan, trachelogenin (TGN), as a potent entry inhibitor of HCV without genotype specificity, and with low cytotoxicity. TGN was extracted and purified from Caulis trachelospermi, a traditional Chinese herb with anti-inflammatory and analgesic effects.

Entry inhibitors: New advances in HCV treatment.

Hepatitis C virus (HCV) infection affects approximately 3% of the world's population and causes chronic liver diseases, including liver fibrosis, cirrhosis, and hepatocellular carcinoma. Although current antiviral therapy comprising direct-acting antivirals (DAAs) can achieve a quite satisfying sustained virological response (SVR) rate, it is still limited by viral resistance, long treatment duration, combined adverse reactions, and high costs. Moreover, the currently marketed antivirals fail to prevent graft reinfections in HCV patients who receive liver transplantations, probably due to the cell-to-cell transmission of the virus, which is also one of the main reasons behind treatment failure.

Anchoring of both PKA-RIIα and 14-3-3θ regulates retinoic acid induced 16 mediated phosphorylation of heat shock protein 70.

Our previous study reported that retinoic acid induced 16 (RAI16) could enhance tumorigenesis in hepatocellular carcinoma (HCC). However, the cellular functions of RAI16 are still unclear. In this study, by immunoprecipitation and tandem (MS/MS) mass spectrometry analysis, we identified that RAI16 interacted with the type II regulatory subunit of PKA (PKA-RIIα), acting as a novel protein kinase A anchoring protein (AKAP).

The role of lipid rafts in the early stage of Enterovirus 71 infection.

Background/aims: Although it has been widely accepted that Enterovirus 71 (EV71) enters permissive cells via receptor-mediated endocytosis, the details of entry mechanism for EV71 still need more exploration. This study aimed to investigate the role of lipid rafts in the early stage of EV71 Infection.

Methods: The effect of cholesterol depletion or addition of exogenous cholesterol was detected by immunofluorescence assays and quantitative real-time PCR.

Two conserved histidines (His490 and His621) on the E2 glycoprotein of hepatitis C virus are critical for CD81-mediated cell entry.

Hepatitis C virus (HCV) entry is a sequential and multi-step process that includes receptor interactions followed by pH-dependent membrane fusion. Specific and conserved histidine residues on the viral envelope proteins are involved in most pH-induced virus entries. In the case of HCV, some conserved histidines on the E1 and E2 proteins have been investigated in HCV pseudotype particle (HCVpp) systems.

Inhibition of IRS-1 by hepatitis C virus infection leads to insulin resistance in a PTEN-dependent manner.

Background: Hepatitis C virus (HCV) infection was recently recognized as an independent risk factor for insulin resistance (IR), the onset phase of type 2 diabetes mellitus (T2DM). Phosphatase and tensin homolog deleted on chromosome 10 (PTEN) negatively regulates PI3K/Akt signaling pathway, which is critical for IR development and progression of cirrhosis to hepatocellular carcinoma (HCC). Here, we investigate the role of PTEN in HCV-associated IR and explored the mechanisms by which HCV regulates PTEN.

Involvement of ERK pathway in interferon alpha-mediated antiviral activity against hepatitis C virus.

Interferon alpha (IFN-α) is the key component of the therapy for hepatitis C virus (HCV) infection. IFN-α exerts anti-HCV activity by targeting certain signaling pathways. Using infectious HCV culture system in human hepatoma Huh7.

HCV infection induces the upregulation of miR-221 in NF-κB dependent manner.

The upregulation of miR-221 has been reported in variety of cancer, including HCV associated HCC, the mechanism of upregulation of miR-221 however remains unclear. In this study, it was found that miR-221 was significantly upregulated in serum of patients with HCV associated chronic hepatitis (cHCV), which suggested the possible biological significance of miR-221 in HCV infection. Important, the upregulated miR-221 was positive correlation with serum miR-122, alanine aminotransferase (ALT) and aspartate transaminase (AST), which are reported as biomarkers for liver injuries.

Small nucleolar RNA 113-1 suppresses tumorigenesis in hepatocellular carcinoma.

Background: Emerging evidence suggests that small nucleolar RNAs (snoRNAs) are involved in tumorigenesis. The roles of small nucleolar RNA 113-1 (SNORD113-1) on the development of hepatocellular carcinoma (HCC) remain unknown.

Methods: The expression of SNORD113-1 was measured in 112 HCC tumor tissues using quantitative RT-PCR and compared with expression levels from with paired non-tumor tissues.

How hepatitis C virus invades hepatocytes: the mystery of viral entry.

Hepatitis C virus (HCV) infection is a global health problem, with an estimated 170 million people being chronically infected. HCV cell entry is a complex multi-step process, involving several cellular factors that trigger virus uptake into the hepatocytes. The high- density lipoprotein receptor scavenger receptor class B type I, tetraspanin CD81, tight junction protein claudin-1, and occludin are the main receptors that mediate the initial step of HCV infection.