Solute Carrier NTCP Regulates Innate Antiviral Immune Responses Targeting Hepatitis C Virus Infection of Hepatocytes

Verrier, Éloi R.; Colpitts, Che C.; Bach, C; Heydmann, Laura; Zona, Laetitia; Xiao, Fei; Thumann, Christine; Crouchet, Émilie; Gaudin, Raphaël; Sureau, Camille; Cosset, François‐Loïc; McKeating, Jane A.; Pessaux, Patrick; Hoshida, Yujin; Schuster, Catherine; Zeisel, Mirjam B.; Baumert, Thomas F.

doi:10.1016/j.celrep.2016.09.084

Cited by 38 publications

(40 citation statements)

References 49 publications

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“…This hypothesis, once tested true, will aid in our efforts towards the establishment of novel cell system for cost-efficient vaccine production that is adaptable to new viral strains or emerging viruses. However, we are aware that viruses presenting totally different types of genome (classified into different Baltimore subtypes) may share the same organ tropism and entry factors such as in the case of HBV and HCV that both target liver and use EGFR (Lupberger et al 2011;Iwamoto et al 2019) and NTCP (Yan et al 2012;Verrier et al 2016) for viral entry, and those belonging to the same Baltimore group may use different receptors for cell entry such as the differential use of HVEM, Nectin 1/2, GFR, CD63, CD151 in mediating the entry of type I viruses besides integrin (Table 1).…”

Section: Opportunities and Challengesmentioning

confidence: 99%

Host receptors: the key to establishing cells with broad viral tropism for vaccine production

Dai

Zhang

Ostrikov

et al. 2020

Critical Reviews in Microbiology

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Cell culture-based vaccine technology is a flexible and convenient approach for vaccine production that requires adaptation of the vaccine strains to the new cells. Driven by the motivation to develop a broadly permissive cell line for infection with a wide range of viruses, we identified a set of the most relevant host receptors involved in viral attachment and entry. This identification was done through a review of different viral entry pathways and host cell lines, and in the context of the Baltimore classification of viruses. In addition, we indicated the potential technical problems and proposed some solutions regarding how to modify the host cell genome in order to meet industrial requirements for mass production of antiviral vaccines. Our work contributes to a finer understanding of the importance of breaking the host-virus recognition specificities for the possibility of creating a cell line feasible for the production of vaccines against a broad spectrum of viruses. ARTICLE HISTORY

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Section: Opportunities and Challengesmentioning

confidence: 99%

Host receptors: the key to establishing cells with broad viral tropism for vaccine production

Dai

Zhang

Ostrikov

et al. 2020

Critical Reviews in Microbiology

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“…Accordingly, transporters have been shown to be modulated during virus infection 4 , are required as viral entry receptors 5,6 or as factors affecting viral cell entry 7,8 . Finally, solute carriers can play important roles in determining the outcome of anti-viral immune responses 9,10 .…”

Section: Introductionmentioning

confidence: 99%

The transporters SLC35A1 and SLC30A1 play opposite roles in cell survival upon VSV virus infection

Moskovskich

Goldmann

Kartnig

et al. 2019

Preprint

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Host factor requirements for different classes of viruses are still to be fully unraveled. Replication of the viral genome and synthesis of viral proteins inside the human host cell are associated with altered, often enhanced, cellular metabolism and increased demand for nutrients as well as specific metabolites. With more than 400 members listed to date in humans, solute carriers (SLCs) represent the largest family of transmembrane proteins dedicated to the transport of ions and small molecules such as amino acids, sugars and nucleotides. Consistent with their impact on cellular metabolism, several SLCs have been implicated as host factors affecting the viral life cycle and the cell response to infection. In this study, we aimed at characterizing the role of host SLCs in cell survival upon viral infection by performing unbiased genetic screens using a focused CRISPR knockout library. Genetic screens with the cytolytic vesicular stomatitis virus (VSV) showed that loss of two SLCs genes, encoding the sialic acid transporter SLC35A1/CST and the zinc transporter SLC30A1/ZnT1, affected cell survival upon infection. Further characterization of these genes pointed to a role of both transporters in the apoptotic response induced by VSV, offering new insights into the cellular response to oncolytic virus infections.

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“…Whereas the antiviral activity of the IFITM proteins against HCV has been studied in cell‐culture models, the role of the IFITM proteins in viral pathogenesis during clinical HCV infection is unknown. It is unclear whether inhibition of virus entry by IFITM proteins contributes to viral clearance, whether IFITM‐HCV interactions impact viral persistence in chronic infection, and whether IFITM proteins and antibodies cooperate to inhibit viral entry.…”

mentioning

confidence: 99%

Interferon‐Induced Transmembrane Proteins Mediate Viral Evasion in Acute and Chronic Hepatitis C Virus Infection

Wrensch¹,

Ligat²,

Heydmann³

et al. 2019

Hepatology

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Although adaptive immune responses against hepatitis C virus (HCV) infection have been studied in great detail, the role of innate immunity in protection against HCV infection and immune evasion is only partially understood.Interferon-induced transmembrane proteins (IFITMs) are innate effector proteins restricting host cell entry of many enveloped viruses, including HCV. However, the clinical impact of IFITMs on HCV immune escape remains to be determined. Here, we show that IFITMs promote viral escape from the neutralizing antibody (nAb) response in clinical cohorts of HCV-infected patients. Using pseudoparticles bearing HCV envelope proteins from acutely infected patients, we show that HCV variants isolated preseroconversion are more sensitive to the antiviral activity of IFITMs than variants from patients isolated during chronic infection postseroconversion. Furthermore, HCV variants escaping nAb responses during liver transplantation exhibited a significantly higher resistance to IFITMs than variants that were eliminated posttransplantation. Gain-of-function and mechanistic studies revealed that IFITMs markedly enhance the antiviral activity of nAbs and suggest a cooperative effect of human monoclonal antibodies and IFITMs for antibody-mediated neutralization driving the selection pressure in viral evasion. Perturbation studies with the IFITM antagonist amphotericin B revealed that modulation of membrane properties by IFITM proteins is responsible for the IFITM-mediated blockade of viral entry and enhancement of antibody-mediated neutralization. Conclusion: Our results indicate IFITM proteins as drivers of viral immune escape and antibodymediated HCV neutralization in acute and chronic HCV infection. These findings are of clinical relevance for the design of urgently needed HCV B-cell vaccines and might help to increase the efficacy of future vaccine candidates.

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Solute Carrier NTCP Regulates Innate Antiviral Immune Responses Targeting Hepatitis C Virus Infection of Hepatocytes

Cited by 38 publications

References 49 publications

Host receptors: the key to establishing cells with broad viral tropism for vaccine production

Host receptors: the key to establishing cells with broad viral tropism for vaccine production

The transporters SLC35A1 and SLC30A1 play opposite roles in cell survival upon VSV virus infection

Interferon‐Induced Transmembrane Proteins Mediate Viral Evasion in Acute and Chronic Hepatitis C Virus Infection

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