Overview of HCV Life Cycle with a Special Focus on Current and Possible Future Antiviral Targets

Alazard-Dany, Nathalie; Denolly, Solène; Boson, Bertrand; Cosset, François‐Loïc

doi:10.3390/v11010030

Cited by 64 publications

(57 citation statements)

References 158 publications

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“…Introduction of DAA‐based therapy leads to a greatly successful rate in which the majority of patients achieve SVR . DAA works by directly targeting specific viral proteins essentially required for viral replication machinery . Insights of the involvement of the host antiviral immunity to mediate viral clearance following DAA therapy are less understood.…”

Section: Functional Reconstitution Of Hbv and Hcv‐specific Immune Resmentioning

confidence: 99%

Expressions of inhibitory checkpoint molecules in acute and chronic HBV and HCV infections: Implications for therapeutic monitoring and personalized therapy

Hakim

Rahmadika

Jariah

2019

Reviews in Medical Virology

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Summary The function of T cells is tightly controlled by positive and negative regulations to ensure both successful pathogen elimination and limitation of immune‐mediated pathology. One of the mechanisms to negatively regulate the magnitude and duration of effector T cells is the expression of inhibitory checkpoint molecules (ICs) on the surface membrane of T cells. During acute viral infections, expression of these molecules is upregulated to limit the effector functions following T‐cell activation. The expression is subsequently downregulated following viral clearance. In contrast, these molecules are continuously expressed in virus‐specific T cells found in persistently infected patients, including cases of chronic hepatitis B virus (HBV) and hepatitis C virus (HCV). The continuously high expression of ICs is responsible for the dysfunctional states of HBV‐ and HCV‐specific T cells in chronic phases, known as T‐cell exhaustion. Hence, understanding the regulation of their expression is essential to give insight into pathogenesis as well as the development of effective immune‐based antiviral therapies. This review discusses recent updated research on expression of ICs during acute and chronic phases of HBV and HCV infections as well as during the clinical course of antiviral therapy.

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Section: Functional Reconstitution Of Hbv and Hcv‐specific Immune Resmentioning

confidence: 99%

Expressions of inhibitory checkpoint molecules in acute and chronic HBV and HCV infections: Implications for therapeutic monitoring and personalized therapy

Hakim

Rahmadika

Jariah

2019

Reviews in Medical Virology

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“…Moreover, inapparent replication of the virus usually results in unnoticed spread of the virus to other individuals, a fact that is a major challenge for surveillance, health care, and treatment [12]. Meanwhile, very effective treatment regimens using direct acting antivirals (DAAs) are available, although they are still very expensive [13,14]. Although the error rate of the viral replicase is high and can, in principle, easily give rise to resistance mutations, the conserved nature of the replicase active center and the often occurring reduced fitness of mutants result in the rare appearance of resistance mutations against nucleoside inhibitors such as sofosbuvir [15,16].…”

Section: Introductionmentioning

confidence: 99%

Hepatitis C Virus Translation Regulation

Niepmann

Gerresheim

2020

IJMS

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Translation of the hepatitis C virus (HCV) RNA genome is regulated by the internal ribosome entry site (IRES), located in the 5’-untranslated region (5′UTR) and part of the core protein coding sequence, and by the 3′UTR. The 5′UTR has some highly conserved structural regions, while others can assume different conformations. The IRES can bind to the ribosomal 40S subunit with high affinity without any other factors. Nevertheless, IRES activity is modulated by additional cis sequences in the viral genome, including the 3′UTR and the cis-acting replication element (CRE). Canonical translation initiation factors (eIFs) are involved in HCV translation initiation, including eIF3, eIF2, eIF1A, eIF5, and eIF5B. Alternatively, under stress conditions and limited eIF2-Met-tRNAiMet availability, alternative initiation factors such as eIF2D, eIF2A, and eIF5B can substitute for eIF2 to allow HCV translation even when cellular mRNA translation is downregulated. In addition, several IRES trans-acting factors (ITAFs) modulate IRES activity by building large networks of RNA-protein and protein–protein interactions, also connecting 5′- and 3′-ends of the viral RNA. Moreover, some ITAFs can act as RNA chaperones that help to position the viral AUG start codon in the ribosomal 40S subunit entry channel. Finally, the liver-specific microRNA-122 (miR-122) stimulates HCV IRES-dependent translation, most likely by stabilizing a certain structure of the IRES that is required for initiation.

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“…The development of an in vitro HCV infection system in 2005 [29,40,41] allowed the identification of viral proteins and cellular factors and pathways that regulate different aspects of the HCV infection (reviewed in [8,42,43]). Using this infection model, we and others have previously identified cellular factors required for initiation of RNA replication [17,32] and HCV assembly and secretion [15,38], and cellular pathways required for the induction [44,45] and evasion [36,46] of the innate immune system.…”

Section: Discussionmentioning

confidence: 99%

“…HCV entry into hepatocytes starts with the interaction of viral and cellular factors, present in the viral membrane, with several receptors present in the plasma membrane of the hepatocytes (reviewed in [8]). These interactions trigger the internalization of HCV via a receptor-mediated endocytosis process that is followed by the fusion of viral and cellular membranes and the release of the viral genome into the cytosol [9].…”

Section: Introductionmentioning

confidence: 99%

The Host Factor Erlin-1 is Required for Efficient Hepatitis C Virus Infection

Whitten-Bauer

Chung

Gómez-Moreno

et al. 2019

Cells

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Development of hepatitis C virus (HCV) infection cell culture systems has permitted the identification of cellular factors that regulate the HCV life cycle. Some of these cellular factors affect steps in the viral life cycle that are tightly associated with intracellular membranes derived from the endoplasmic reticulum (ER). Here, we describe the discovery of erlin-1 protein as a cellular factor that regulates HCV infection. Erlin-1 is a cholesterol-binding protein located in detergent-resistant membranes within the ER. It is implicated in cholesterol homeostasis and the ER-associated degradation pathway. Silencing of erlin-1 protein expression by siRNA led to decreased infection efficiency characterized by reduction in intracellular RNA accumulation, HCV protein expression and virus production. Mechanistic studies revealed that erlin-1 protein is required early in the infection, downstream of cell entry and primary translation, specifically to initiate RNA replication, and later in the infection to support infectious virus production. This study identifies erlin-1 protein as an important cellular factor regulating HCV infection.

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Overview of HCV Life Cycle with a Special Focus on Current and Possible Future Antiviral Targets

Cited by 64 publications

References 158 publications

Expressions of inhibitory checkpoint molecules in acute and chronic HBV and HCV infections: Implications for therapeutic monitoring and personalized therapy

Expressions of inhibitory checkpoint molecules in acute and chronic HBV and HCV infections: Implications for therapeutic monitoring and personalized therapy

Hepatitis C Virus Translation Regulation

The Host Factor Erlin-1 is Required for Efficient Hepatitis C Virus Infection

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