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Current Topics in Microbiology and... 2013Hepatitis C virus (HCV) is a hepatotropic virus and a major cause of chronic hepatitis and liver disease worldwide. Initial interactions between HCV virions and... (Review)
Review
Hepatitis C virus (HCV) is a hepatotropic virus and a major cause of chronic hepatitis and liver disease worldwide. Initial interactions between HCV virions and hepatocytes are required for productive viral infection and initiation of the viral life cycle. Furthermore, HCV entry contributes to the tissue tropism and species specificity of this virus. The elucidation of these interactions is critical, not only to understand the pathogenesis of HCV infection, but also to design efficient antiviral strategies and vaccines. This review summarizes our current knowledge of the host factors required for the HCV-host interactions during HCV binding and entry, our understanding of the molecular mechanisms underlying HCV entry into target cells, and the relevance of HCV entry for the pathogenesis of liver disease, antiviral therapy, and vaccine development.
Topics: Animals; Antiviral Agents; Hepacivirus; Hepatitis C; Host-Pathogen Interactions; Humans; Virus Attachment; Virus Internalization
PubMed: 23463198
DOI: 10.1007/978-3-642-27340-7_4 -
World Journal of Gastroenterology Nov 2014Hepatitis C virus (HCV) infection represents an important public health problem worldwide. Reduction of HCV morbidity and mortality is a current challenge owned to... (Review)
Review
Hepatitis C virus (HCV) infection represents an important public health problem worldwide. Reduction of HCV morbidity and mortality is a current challenge owned to several viral and host factors. Virus molecular evolution plays an important role in HCV transmission, disease progression and therapy outcome. The high degree of genetic heterogeneity characteristic of HCV is a key element for the rapid adaptation of the intrahost viral population to different selection pressures (e.g., host immune responses and antiviral therapy). HCV molecular evolution is shaped by different mechanisms including a high mutation rate, genetic bottlenecks, genetic drift, recombination, temporal variations and compartmentalization. These evolutionary processes constantly rearrange the composition of the HCV intrahost population in a staging manner. Remarkable advances in the understanding of the molecular mechanism controlling HCV replication have facilitated the development of a plethora of direct-acting antiviral agents against HCV. As a result, superior sustained viral responses have been attained. The rapidly evolving field of anti-HCV therapy is expected to broad its landscape even further with newer, more potent antivirals, bringing us one step closer to the interferon-free era.
Topics: Animals; Antiviral Agents; Disease Progression; Drug Resistance, Viral; Drug Therapy, Combination; Evolution, Molecular; Genotype; Hepacivirus; Hepatitis C; Host-Pathogen Interactions; Humans; Phenotype; Treatment Outcome
PubMed: 25473152
DOI: 10.3748/wjg.v20.i43.15992 -
Journal of Hepatology Nov 2014Hepatitis C virus (HCV) is an important human pathogen that causes hepatitis, liver cirrhosis and hepatocellular carcinoma. It imposes a serious problem to public health... (Review)
Review
Hepatitis C virus (HCV) is an important human pathogen that causes hepatitis, liver cirrhosis and hepatocellular carcinoma. It imposes a serious problem to public health in the world as the population of chronically infected HCV patients who are at risk of progressive liver disease is projected to increase significantly in the next decades. However, the arrival of new antiviral molecules is progressively changing the landscape of hepatitis C treatment. The search for new anti-HCV therapies has also been a driving force to better understand how HCV interacts with its host, and major progresses have been made on the various steps of the HCV life cycle. Here, we review the most recent advances in the fast growing knowledge on HCV life cycle and interaction with host factors and pathways.
Topics: Cell Biology; Hepacivirus; Hepatitis C; Hepatocytes; Humans; Life Cycle Stages; Lipid Metabolism; RNA, Viral; Virology; Virus Replication
PubMed: 25443344
DOI: 10.1016/j.jhep.2014.06.031 -
Viruses Aug 2017Autophagy is a catabolic process that is important for maintaining cellular homeostasis. This pathway in hepatocytes is stimulated and controlled by the hepatitis C... (Review)
Review
Autophagy is a catabolic process that is important for maintaining cellular homeostasis. This pathway in hepatocytes is stimulated and controlled by the hepatitis C virus (HCV)-upon infection-to promote its own replication. HCV induces autophagy indirectly and directly through different mechanisms and temporally controls the autophagic flux. This enables the virus to maximize its replication and attenuate the innate immune responses that it activates. In this review, we discuss the relationship between HCV and autophagy, and the crosstalk between HCV-induced autophagy and host innate immune responses.
Topics: Animals; Autophagy; Hepacivirus; Hepatitis C; Humans; Immunity, Innate; Virus Replication
PubMed: 28805674
DOI: 10.3390/v9080224 -
Biological Chemistry Nov 2015Autophagy is a catabolic process by which cells remove protein aggregates and damaged organelles for recycling. It can also be used by cells to remove intracellular... (Review)
Review
Autophagy is a catabolic process by which cells remove protein aggregates and damaged organelles for recycling. It can also be used by cells to remove intracellular microbial pathogens, including viruses, in a process known as xenophagy. However, many viruses have developed mechanisms to subvert this intracellular antiviral response and even use this pathway to support their own replications. Hepatitis C virus (HCV) is one such virus and is an important human pathogen that can cause severe liver diseases. Recent studies indicated that HCV could activate the autophagic pathway to support its replication. This review summarizes the current knowledge on the interplay between HCV and autophagy and how this interplay affects HCV replication and host innate immune responses.
Topics: Animals; Autophagy; Hepacivirus; Humans; Immunity, Innate; Virus Replication
PubMed: 26024249
DOI: 10.1515/hsz-2015-0172 -
Cold Spring Harbor Perspectives in... Mar 2020Replication and amplification of the viral genome is a key process for all viruses. For hepatitis C virus (HCV), a positive-strand RNA virus, amplification of the viral... (Review)
Review
Replication and amplification of the viral genome is a key process for all viruses. For hepatitis C virus (HCV), a positive-strand RNA virus, amplification of the viral genome requires the synthesis of a negative-sense RNA template, which is in turn used for the production of new genomic RNA. This process is governed by numerous proteins, both host and viral, as well as distinct lipids and specific RNA elements within the positive- and negative-strand RNAs. Moreover, this process requires specific changes to host cell ultrastructure to create microenvironments conducive to viral replication. This review will focus on describing the processes and factors involved in facilitating or regulating HCV genome replication.
Topics: Genes, Viral; Genome, Viral; Hepacivirus; Humans; RNA, Viral; Viral Proteins; Viral Structural Proteins; Virus Replication
PubMed: 31570388
DOI: 10.1101/cshperspect.a037093 -
World Journal of Gastroenterology Jun 2014Hepatitis C virus (HCV) is a major cause of chronic liver diseases, including steatosis, cirrhosis and hepatocellular carcinoma, and its infection is also associated... (Review)
Review
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 protein-coding 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.
Topics: Animals; Antiviral Agents; Drug Design; Hepacivirus; Hepatitis C; Host-Pathogen Interactions; Humans; Liver; Molecular Targeted Therapy; Signal Transduction; Viral Core Proteins; Virulence Factors
PubMed: 24966583
DOI: 10.3748/wjg.v20.i23.7104 -
Annals of Hepatology 2015Hepatitis C virus (HCV) has a short replication time, high mutation rates and large population sizes, all of which make it an excellent experimental model for evolution... (Review)
Review
Hepatitis C virus (HCV) has a short replication time, high mutation rates and large population sizes, all of which make it an excellent experimental model for evolution studies, because evolution can be visualized in real-time. In this review, we discuss the implications to study HCV evolution at the interpatient and intrapatient levels of infection. The HCV interpatient dynamics is relatively slow, because the generation time is generally long. Then, at population level, the HCV diversity originated by the high mutation and replication rates is modulated by the bottleneck at transmission. Thus, when the virus is transmitted to other hosts, viral diversity is reduced as a result of the founder effect. On the other hand, during intrapatient infection, HCV evolves rapidly, resulting in quasispecies. Accumulated evidence suggests that this quasispecies composition of the HCV population within the same individual may allow the virus to evade the immune response or escape treatment, leading to chronic infection. Thus, a better understanding of the complexities underlying the molecular evolution of HCV in natural populations is needed before accurate predictions of viral evolution can be made. In summary, HCV evolves both within and among patients. Consequently, HCV evolution should be studied at both levels in order to better understand the natural history of the virus and its potential implications in epidemiology, outcome of infection and progression of liver disease.
Topics: Antiviral Agents; Drug Resistance, Viral; Evolution, Molecular; Genotype; Hepacivirus; Hepatitis C; Humans; Immune Evasion; Mutation; Phenotype; Time Factors; Virus Replication
PubMed: 26019029
DOI: No ID Found -
Current Opinion in Virology Dec 2012As a relatively simple virus, hepatitis C virus (HCV) depends extensively on its host to infect, replicate and disseminate. HCV has evolved host interactions that result... (Review)
Review
As a relatively simple virus, hepatitis C virus (HCV) depends extensively on its host to infect, replicate and disseminate. HCV has evolved host interactions that result in a restricted tropism, both in terms of cell type and species. Efforts into identifying and validating HCV-host interactions have been hampered by a limited number of infectious virus clones and cell lines that support HCV infection. Despite these limitations, consensus HCV-host interactions have emerged that help define the entry, replication, assembly, and tropism of HCV. This has had important implications in expanding our in vitro and in vivo systems to study HCV replication and pathogenesis. Additionally, a number of these host factors are being targeted for therapeutic development. In this review, we focus on medically relevant pro-viral host factors, their role in HCV biology, and their importance in expanding our model systems.
Topics: Hepacivirus; Host-Pathogen Interactions; Humans; Viral Tropism; Virus Assembly; Virus Internalization; Virus Replication
PubMed: 23083892
DOI: 10.1016/j.coviro.2012.09.013 -
Viruses Aug 2015The high prevalence of hepatitis C virus (HCV) infection in the human population has triggered intensive research efforts that have led to the development of curative... (Review)
Review
The high prevalence of hepatitis C virus (HCV) infection in the human population has triggered intensive research efforts that have led to the development of curative antiviral therapy. Moreover, HCV has become a role model to study fundamental principles that govern the replication cycle of a positive strand RNA virus. In fact, for most HCV proteins high-resolution X-ray and NMR (Nuclear Magnetic Resonance)-based structures have been established and profound insights into their biochemical and biological properties have been gained. One example is p7, a small hydrophobic protein that is dispensable for RNA replication, but crucial for the production and release of infectious HCV particles from infected cells. Owing to its ability to insert into membranes and assemble into homo-oligomeric complexes that function as minimalistic ion channels, HCV p7 is a member of the viroporin family. This review compiles the most recent findings related to the structure and dual pore/ion channel activity of p7 of different HCV genotypes. The alternative conformations and topologies proposed for HCV p7 in its monomeric and oligomeric state are described and discussed in detail. We also summarize the different roles p7 might play in the HCV replication cycle and highlight both the ion channel/pore-like function and the additional roles of p7 unrelated to its channel activity. Finally, we discuss possibilities to utilize viroporin inhibitors for antagonizing p7 ion channel/pore-like activity.
Topics: Hepacivirus; Humans; Models, Molecular; Protein Conformation; Viral Proteins; Virus Assembly; Virus Release
PubMed: 26258788
DOI: 10.3390/v7082826