Hepatitis C virus articles within Nature Communications

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• Article
  22 January 2024 | Open Access

  EGFR core fucosylation, induced by hepatitis C virus, promotes TRIM40-mediated-RIG-I ubiquitination and suppresses interferon-I antiviral defenses

  Alpha-(1,6)-fucosyltransferase (FUT8) is the sole enzyme responsible for core fucosylation of N-glycans during glycoprotein biosynthesis. Here the authors show that HCV envelope protein E2 enhances FUT8 expression through the EGFR-AKT-SNAIL axis, which subsequently promotes RIG-I K48-ubiquitination and dampens the antiviral IFN-I response through core fucosylated-EGFR-JAK1-STAT3-RIG-I pathway.

  • Qiu Pan
  • , Yan Xie
  •  & Xiao-Lian Zhang

• Article
  17 November 2023 | Open Access

  Direct-acting antiviral resistance of Hepatitis C virus is promoted by epistasis

  This study reveals that mutations of the hepatitis C virus act collectively to confer resistance against direct-acting antiviral drugs. This can aid the development of drugs that are less prone to resistance.

  • Hang Zhang
  • , Ahmed Abdul Quadeer
  •  & Matthew R. McKay

• Article
  07 July 2023 | Open Access

  Signatures of V_H1-69-derived hepatitis C virus neutralizing antibody precursors defined by binding to envelope glycoproteins

  The burden of chronic hepatitis C virus infection is exacerbated by the lack of an effective vaccine. In this work, authors use a recombinant permuted (E2E1) HCV glycoprotein design to analyze the binding of different VH1-69-derived AR3-directed broadly neutralizing antibodies to the viral envelope glycoprotein.

  • Joan Capella-Pujol
  • , Marlon de Gast
  •  & Kwinten Sliepen

• Article
  05 July 2023 | Open Access

  Structure of engineered hepatitis C virus E1E2 ectodomain in complex with neutralizing antibodies

  HCV vaccine development has been challenged by difficulties in the biochemical preparation of E1E2 ectodomains. Here, the authors structurally characterize an engineered soluble E1E2 ectodomain complexed with broadly neutralizing antibodies, revealing it adopts a native fold amenable for vaccine design.

  • Matthew C. Metcalf
  • , Benjamin M. Janus
  •  & Gilad Ofek

• Article
  26 January 2023 | Open Access

  Regions of hepatitis C virus E2 required for membrane association

  Hepatitis C virus (HCV) uses a hybrid entry mechanism. Upon exposure to low pH, envelope glycoprotein E2 releases an internal loop into the host membrane. Here we show the amino terminal region is a critical determinant for membrane interaction, providing insights into the HCV entry mechanism.

  • Ashish Kumar
  • , Tiana C. Rohe
  •  & Joseph Marcotrigiano

• Article
  07 December 2022 | Open Access

  Identification of human progenitors of exhausted CD8⁺ T cells associated with elevated IFN-γ response in early phase of viral infection

  The early immune response following exposure to HCV is not fully explored. Here the authors use single cell analysis and immune profiling to relate the infection sequence and immune response to early HCV infection showing that exhausted phenotypes of T cells arise early post infection.

  • Curtis Cai
  • , Jerome Samir
  •  & Fabio Luciani

• Article
  25 November 2022 | Open Access

  Induction of cross-neutralizing antibodies by a permuted hepatitis C virus glycoprotein nanoparticle vaccine candidate

  E1E2 spike on the hepatitis C virion is an important target for vaccine design. Here, the authors permute the subunits to generate E2E1 immunogens and show that mosaic nanoparticles displaying different E2E1 antigens elicit cross-neutralizing antibodies in rabbits.

  • Kwinten Sliepen
  • , Laura Radić
  •  & Rogier W. Sanders

• Article
  16 September 2022 | Open Access

  Serum neutralization activity declines but memory B cells persist after cure of chronic hepatitis C

  Long-term dynamics of the humoral response to HCV in cured individuals aren’t well understood. Here, Nishio et al. show that virus-neutralizing antibody levels decrease in potency and breadth after cure of chronic hepatitis C, while HCV-specific memory B cells persist.

  • Akira Nishio
  • , Sharika Hasan
  •  & Barbara Rehermann

• Article
  14 December 2021 | Open Access

  Convergent use of phosphatidic acid for hepatitis C virus and SARS-CoV-2 replication organelle formation

  Double membrane vesicles (DMV) are used as replication organelles by several RNA viruses. Applying proteomics and lipidomics, Tabata and Prasad et al. find that two cellular acyltransferases (AGPAT1/2), responsible for synthesis of phosphatidic acid, play a role in the DMV-biogenesis of HCV and SARS-CoV-2, highlighting a common biogenesis mechanism for evolutionary distant positive-strand RNA viruses.

  • Keisuke Tabata
  • , Vibhu Prasad
  •  & Ralf Bartenschlager

• Article
  30 November 2021 | Open Access

  Paper microfluidic implementation of loop mediated isothermal amplification for early diagnosis of hepatitis C virus

  Current HCV nucleic acid-based diagnosis is largely performed in centralised laboratories. Here, the authors present a pan-genotypic RNA assay, based on reverse transcriptase loop mediated isothermal amplification and develop a low-cost prototype paper-based lateral flow device for point-of-care use, providing a visually read result within 40 min.

  • Weronika Witkowska McConnell
  • , Chris Davis
  •  & Jonathan M. Cooper

• Article
  25 November 2021 | Open Access

  A structured RNA motif locks Argonaute2:miR-122 onto the 5’ end of the HCV genome

  The RNA genome of the Hepatitis C Virus binds to the liver-specific miR122. Here the authors report the crystal structure of the Ago2:miR122:HCV complex showing that the viral RNA’s structural element traps the Ago2:miR-122 complex on the 5’ end of the viral genome to protect it from degradation.

  • Luca F. R. Gebert
  • , Mansun Law
  •  & Ian J. MacRae

• Article
  25 November 2021 | Open Access

  Plasma virome and the risk of blood-borne infection in persons with substance use disorder

  Spread of bloodborne infections, such as HCV and HIV, is a problem, particularly amongst people who inject drugs (PWID). Here, the authors describe and then confirm in observational PWID cohorts that those with more non-pathogenic viruses in plasma were more likely later to acquire HCV than PWID who had fewer of these non-pathogenic viruses.

  • Abraham J. Kandathil
  • , Andrea L. Cox
  •  & David L. Thomas

• Article
  20 October 2021 | Open Access

  Viral genome wide association study identifies novel hepatitis C virus polymorphisms associated with sofosbuvir treatment failure

  Sofosbuvir is a common therapy in hepatitis C virus infection, which targets the NS5B polymerase. Here, Smith et al. analyze the association between whole genome HCV polymorphisms and sofosbuvir treatment failure and identify three common polymorphisms present in non-targeted NS2 and NS3 proteins associated with reduced treatment response.

  • David A. Smith
  • , Carlota Fernandez-Antunez
  •  & M. Azim Ansari

• Article
  12 August 2021 | Open Access

  Interferon lambda 4 impairs hepatitis C viral antigen presentation and attenuates T cell responses

  A genetic variant in the IFN-lambda 4 gene has been associated with poor hepatitis C virus prognosis but it is not clear how this functions. Here the authors show that IFN-lambda 4 promotes ER stress and inhibits presentation of HCV epitopes to CD8⁺ T cells.

  • Qian Chen
  • , Mairene Coto-Llerena
  •  & Markus H. Heim

• Article
  17 June 2020 | Open Access

  p53 destabilizing protein skews asymmetric division and enhances NOTCH activation to direct self-renewal of TICs

  Normal stem cells are maintained by asymmetric cell division, but this process is dysregulated in tumour initiating stem-like cells (TICs). Here, the authors show that TBC1D15 impairs the asymmetric division machinery and activates NOTCH pathway for TIC self-renewal and expansion to promote liver tumorigenesis.

  • Hye Yeon Choi
  • , Hifzur R. Siddique
  •  & Keigo Machida

• Article
  01 August 2019 | Open Access

  Small molecule degraders of the hepatitis C virus protease reduce susceptibility to resistance mutations

  Targeted protein degradation (TPD) is a promising strategy for drug development. In this proof-of-concept study, the authors use telaprevir, which binds hepatitis C virus (HCV) NS3/4A protease, to target the protease for protein degradation, and show inhibition of wildtype as well as drug resistant HCV.

  • Mélissanne de Wispelaere
  • , Guangyan Du
  •  & Priscilla L. Yang

• Article
  08 May 2019 | Open Access

  Enveloped viruses distinct from HBV induce dissemination of hepatitis D virus in vivo

  Hepatitis D virus (HDV) relies on a helper virus to package and transmit its ribonucleoprotein (RNP). Here, Perez-Vargas et al. show that HDV can use envelope proteins from HBV-unrelated viruses, including HCV and flaviviruses, to propagate in vitro and in humanized mice.

  • Jimena Perez-Vargas
  • , Fouzia Amirache
  •  & François-Loïc Cosset

• Article
  06 May 2019 | Open Access

  Identifying immunologically-vulnerable regions of the HCV E2 glycoprotein and broadly neutralizing antibodies that target them

  A good vaccine should direct the immune response to virus regions that are most difficult to escape. Here, Quadeer et al. develop a predictive in-silico evolutionary model for HCV E2 which identifies one such antigenic region and identifies multiple broadly neutralizing human antibodies that appear difficult to escape from.

  • Ahmed A. Quadeer
  • , Raymond H. Y. Louie
  •  & Matthew R. McKay

• Article
  07 March 2019 | Open Access

  Vaccination to prevent T cell subversion can protect against persistent hepacivirus infection

  Development of a HCV vaccine is hampered by a lack of appropriate small animal models. Here, Hartlage et al. describe a rat model of hepacivirus persistence and show that persistence can be prevented by vaccination with viral non-structural proteins.

  • Alex S. Hartlage
  • , Satyapramod Murthy
  •  & Amit Kapoor

• Article
  29 January 2019 | Open Access

  Inactivating hepatitis C virus in donor lungs using light therapies during normothermic ex vivo lung perfusion

  Organs from donors with transmissible viral infections, such as hepatitis C virus (HCV), are not offered for transplantation due to a high risk of transmission. Here, Galasso et al. develop a method for treatment of HCV-infected human donor lungs that is safe and prevents HCV transmission in the pig model.

  • Marcos Galasso
  • , Jordan J. Feld
  •  & Marcelo Cypel

• Article
  22 January 2019 | Open Access

  The circadian clock components BMAL1 and REV-ERBα regulate flavivirus replication

  The circadian clock can affect pathogen replication, but underlying molecular mechanisms are unclear. Here the authors demonstrate that the circadian components BMAL1 and REV-ERBα affect entry of hepatitis C virus (HCV) into hepatocytes and genome replication of HCV and related flaviviruses dengue and zika.

  • Xiaodong Zhuang
  • , Andrea Magri
  •  & Jane A. McKeating

• Article
  23 April 2018 | Open Access

  Vibrio vulnificus quorum-sensing molecule cyclo(Phe-Pro) inhibits RIG-I-mediated antiviral innate immunity

  Quorum sensing signaling molecules are known to be critical determinants in bacterial pathogenesis. Here the authors show the quorum sensing molecule cFP from Vibrio vulnificus inhibits the RIG-I mediated antiviral interferon response and enhances susceptibility to viral infection.

  • Wooseong Lee
  • , Seung-Hoon Lee
  •  & Jong-Won Oh

• Article
  27 November 2017 | Open Access

  Cellular microRNA networks regulate host dependency of hepatitis C virus infection

  Using genome-wide miRNA mimic and hairpin inhibitor screens, Li et al. identify 31 miRNAs that either inhibit or promote hepatitis C virus (HCV) replication at different steps of the viral life cycle. Furthermore, human liver biopsies show that HCV down-regulates identified miRNAs with antiviral function.

  • Qisheng Li
  • , Brianna Lowey
  •  & T. Jake Liang

• Article
  08 May 2017 | Open Access

  Signalome-wide assessment of host cell response to hepatitis C virus

  Development of antiviral strategies depends on an understanding of virus–host interactions. Here, using HCV, Haqshenaset al. show that antibody microarray combined with a targeted siRNA screen can be a powerful tool to identify cellular signalling pathways that are important for virus replication.

  • Gholamreza Haqshenas
  • , Jianmin Wu
  •  & Christian Doerig

• Article
  09 January 2017 | Open Access

  Hepatitis C virus has a genetically determined lymphotropism through co-receptor B7.2

  Infection of B cells by hepatitis C virus (HCV) is poorly understood, but is thought to result in lymphoproliferative disorders. Here, Chenet al. identify CD86 as co-receptor for lymphotropic HCV and show that HCV infection inhibits memory B-cell function.

  • Chia-Lin Chen
  • , Jeffrey Y. Huang
  •  & Keigo Machida

• Article
  04 May 2016 | Open Access

  TRC8-dependent degradation of hepatitis C virus immature core protein regulates viral propagation and pathogenesis

  A cellular protease, SPP, participates in production of the mature core protein of hepatitis C virus (HCV). Here, the authors show in mouse models that SPP inhibition reduces viral propagation and pathogenesis via proteasomal degradation of the immature core protein mediated by the E3 ubiquitin ligase TRC8.

  • Sayaka Aizawa
  • , Toru Okamoto
  •  & Yoshiharu Matsuura

• Article
  12 February 2016 | Open Access

  Interferon-inducible protein SCOTIN interferes with HCV replication through the autolysosomal degradation of NS5A

  Hepatitis C virus (HCV) nonstructural 5A (NS5A) protein is a critical factor for HCV RNA replication. Here the authors show that SCOTIN, an interferon beta-inducible host protein, functions to limit HCV replication by targeting viral protein NS5A for autophagosomal degradation.

  • Nari Kim
  • , Min-Jung Kim
  •  & Joo-Yeon Yoo

• Article | 23 December 2014

  Reduced IFNλ4 activity is associated with improved HCV clearance and reduced expression of interferon-stimulated genes

  Genetic variation in the IFNλ locus has been associated with clearance of hepatitis C virus. Here, the authors show that a single amino-acid variant of IFNλ4 affects its antiviral activity and that patients carrying the impaired variant have better viral clearance rates.

  • Ewa Terczyńska-Dyla
  • , Stephanie Bibert
  •  & Rune Hartmann

• Article | 18 November 2014

  Hepatitis C virus genetics affects miR-122 requirements and response to miR-122 inhibitors

  Replication of the hepatitis C virus (HCV) requires a host RNA molecule, miR-122, whose transient inhibition is being explored as an antiviral therapy. Here, the authors study the interaction between miR-122 and HCV, and identify mutations in HCV strains that affect susceptibility to miR-122 inhibition.

  • Benjamin Israelow
  • , Gavriel Mullokandov
  •  & Matthew J. Evans

• Article | 19 March 2013

  Structure of the full-length HCV IRES in solution

  The hepatitis C virus RNA genome is translated via an internal ribosome entry site. Pérard et al. present an atomic model of this site, and using molecular dynamics simulations, identify conformational flexibility that may underlie its function during translation initiation.

  • Julien Pérard
  • , Cédric Leyrat
  •  & Marc Jamin