Cellular factors involved in the hepatitis C virus life cycle

The hepatitis C virus(HCV),an obligatory intracellular pathogen,highly depends on its host cells to propagate successfully.The HCV life cycle can be simply divided into several stages including viral entry,protein translation,RNA replication,viral assembly and release.Hundreds of cellular factors involved in the HCV life cycle have been identified over more than thirty years of research.Characterization of these cellular factors has provided extensive insight into HCV replication strategies.Some of these cellular factors are targets for anti-HCV therapies.In this review,we summarize the well-characterized and recently identified cellular factors functioning at each stage of the HCV life cycle.

Long noncoding RNAs in hepatitis B virus replication and oncogenesis

Several diverse long noncoding RNAs(lncRNAs)have been identified to be involved in hepatitis B virus(HBV)replication and oncogenesis,especially those dysregulated in HBV-related hepatocellular carcinoma(HCC).Most of these dysregulated lncRNAs are modulated by the HBV X protein.The regulatory mechanisms of some lncRNAs in HBV replication and oncogenesis have been characterized.Genetic polymorphisms of several lncRNAs affecting HBV replication or oncogenesis have also been studied.The prognosis of HCC remains poor.It is important to identify novel tumor markers for early diagnosis and find more therapeutic targets for effective treatments of HCC.Some dysregulated lncRNAs in HBV-related HCC may become biomarkers for early diagnosis and/or the therapeutic targets of HCC.This mini-review summarizes these findings briefly,focusing on recent developments.

Production and pathogenicity of hepatitis C virus core gene products

Hepatitis C virus(HCV)is a major cause of chronic liver diseases,including steatosis,cirrhosis and hepatocellular carcinoma,and its infection is also associated with insulin resistance and type 2 diabetes mellitus.HCV,belonging to the Flaviviridae family,is a small enveloped virus whose positive-stranded RNA genome encoding a polyprotein.The HCV core protein is cleaved first at residue 191 by the host signal peptidase and further cleaved by the host signal peptide peptidase at about residue 177 to generate the mature core protein(a.a.1-177)and the cleaved peptide(a.a.178-191).Core protein could induce insulin resistance,steatosis and even hepatocellular carcinoma through various mechanisms.The peptide(a.a.178-191)may play a role in the immune response.The polymorphism of this peptide is associated with the cellular lipid drop accumulation,contributing to steatosis development.In addition to the conventional open reading frame(ORF),in the+1 frame,an ORF overlaps with the core proteincoding sequence and encodes the alternative reading frame proteins(ARFP or core+1).ARFP/core+1/F protein could enhance hepatocyte growth and may regulate iron metabolism.In this review,we briefly summarized the current knowledge regarding the production of different core gene products and their roles in viral pathogenesis.

Hepatitis C virus:Virology,diagnosis and treatment

More than twenty years of study has provided a better understanding of hepatitis C virus(HCV) life cycle,including the general properties of viral RNA and proteins. This effort facilitates the development of sensitive diagnostic tools and effective antiviraltreatments. At present,serologic screening test is recommended to perform on individuals in the high risk groups and nucleic acid tests are recommended to confirm the active HCV infections. Quantization and genotyping of HCV RNAs are important to determine the optimal duration of anti-viral therapy and predict the likelihood of response. In the early 2000 s,pegylated interferon plus ribavirin became the standard antiHCV treatment. However,this therapy is not ideal. To 2014,boceprevir,telaprevir,simeprevir,sofosbuvir and Harvoni are approved by Food and Drug Administration for the treat of HCV infections. It is likely that the new all-oral,interferon-free,pan-genotyping anti-HCV therapy will be available within the next few years. Majority of HCV infections will be cured by these antiviral treatments. However,not all patients are expected to be cured due to viral resistance and the high cost of antiviral treatments. Thus,an efficient prophylactic vaccine will be the next challenge in the fight against HCV infection.