Taming a beast: lessons from the domestication of hepatitis C virus

Luna, Joseph M.; Saeed, Mohsan; Rice, Charles M.

doi:10.1016/j.coviro.2019.02.008

Cited by 10 publications

(7 citation statements)

References 98 publications

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“…It is worthy to note the pivotal role of replicon systems in discovering HCV replication inhibitors, as previously reviewed by [ 35 , 40 ] and more recently by [ 41 , 42 ]. Since the establishment of the first HCV replicon system in 1999 by Bartenschlager’s group [ 43 ], when a functional replicon was developed from a genotype 1a isolate using Huh7 cells, HCV replicons have been improved by exploring distinct permissive cell lines, virus genotypes, adaptive mutations, and their relation with drug resistance.…”

Section: Enveloped Rna Virusesmentioning

confidence: 99%

Reporter Replicons for Antiviral Drug Discovery against Positive Single-Stranded RNA Viruses

Fernandes

Freire

Bueno

et al. 2020

Viruses

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Single-stranded positive RNA ((+) ssRNA) viruses include several important human pathogens. Some members are responsible for large outbreaks, such as Zika virus, West Nile virus, SARS-CoV, and SARS-CoV-2, while others are endemic, causing an enormous global health burden. Since vaccines or specific treatments are not available for most viral infections, the discovery of direct-acting antivirals (DAA) is an urgent need. Still, the low-throughput nature of and biosafety concerns related to traditional antiviral assays hinders the discovery of new inhibitors. With the advances of reverse genetics, reporter replicon systems have become an alternative tool for the screening of DAAs. Herein, we review decades of the use of (+) ssRNA viruses replicon systems for the discovery of antiviral agents. We summarize different strategies used to develop those systems, as well as highlight some of the most promising inhibitors identified by the method. Despite the genetic alterations introduced, reporter replicons have been shown to be reliable systems for screening and identification of viral replication inhibitors and, therefore, an important tool for the discovery of new DAAs.

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Section: Enveloped Rna Virusesmentioning

confidence: 99%

Reporter Replicons for Antiviral Drug Discovery against Positive Single-Stranded RNA Viruses

Fernandes

Freire

Bueno

et al. 2020

Viruses

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“…In 2020 the Nobel Prize in Physiology or Medicine was awarded to the Americans Harvey J Alter (United States National Institutes of Health) and Charles M Rice (Rockefeller University) and to the British Michael Houghton (University of Alberta) for the discovery of the HCV. Alter demonstrated the existence of a non-A non-B hepatitis virus-associated with post-transfusion hepatitis in 1975, Houghton cloned and identified the viral genome and renamed it as HCV in 1989, and Rice established, from an edited version of the virus genome, a robust in vitro replication system in cell cultures in the 1990s and thus laid the foundation for future genetic and functional analysis[ 84 - 86 ].…”

Section: Hcvmentioning

confidence: 99%

Viral hepatitis update: Progress and perspectives

Pisano¹,

Giadans²,

Flichman³

et al. 2021

WJG

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Viral hepatitis, secondary to infection with hepatitis A, B, C, D, and E viruses, are a major public health problem and an important cause of morbidity and mortality. Despite the huge medical advances achieved in recent years, there are still points of conflict concerning the pathogenesis, immune response, development of new and more effective vaccines, therapies, and treatment. This review focuses on the most important research topics that deal with issues that are currently being solved, those that remain to be solved, and future research directions. For hepatitis A virus we will address epidemiology, molecular surveillance, new susceptible populations as well as environmental and food detections. In the case of hepatitis B virus, we will discuss host factors related to disease, diagnosis, therapy, and vaccine improvement. On hepatitis C virus, we will focus on pathogenesis, immune response, direct action antivirals treatment in the context of solid organ transplantation, issues related to hepatocellular carcinoma development, direct action antivirals resistance due to selection of resistance-associated variants, and vaccination. Regarding hepatitis D virus, we describe diagnostic methodology, pathogenesis, and therapy. Finally, for hepatitis E virus, we will address epidemiology (including new emerging species), diagnosis, clinical aspects, treatment, the development of a vaccine, and environmental surveillance.

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“…Nevertheless, despite this breakthrough, efforts to replicate this with other isolates corresponding to different genotypes were only partially successful. On the one hand, some of these cloned full-length RNAs were able to produce infection in vivo (in chimpanzees), but on the other hand, even in the presence of multiple adaptive mutations, they failed to produce infectious viral particles in cell culture, despite some being able to efficiently replicate (details on the history of HCV cell culture systems are thoroughly reviewed elsewhere[ 147 , 152 - 154 ]).…”

Section: Challenges For Developing Anti-hcv Vaccinesmentioning

confidence: 99%

In the era of rapid mRNA-based vaccines: Why is there no effective hepatitis C virus vaccine yet?

Echeverría¹,

Comas²,

Aldunate³

et al. 2021

WJH

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Hepatitis C virus (HCV) is responsible for no less than 71 million people chronically infected and is one of the most frequent indications for liver transplantation worldwide. Despite direct-acting antiviral therapies fuel optimism in controlling HCV infections, there are several obstacles regarding treatment accessibility and reinfection continues to remain a possibility. Indeed, the majority of new HCV infections in developed countries occur in people who inject drugs and are more plausible to get reinfected. To achieve global epidemic control of this virus the development of an effective prophylactic or therapeutic vaccine becomes a must. The coronavirus disease 19 (COVID-19) pandemic led to auspicious vaccine development against severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) virus, which has renewed interest on fighting HCV epidemic with vaccination. The aim of this review is to highlight the current situation of HCV vaccine candidates designed to prevent and/or to reduce HCV infectious cases and their complications. We will emphasize on some of the crossroads encountered during vaccine development against this insidious virus, together with some key aspects of HCV immunology which have, so far, hampered the progress in this area. The main focus will be on nucleic acid-based as well as recombinant viral vector-based vaccine candidates as the most novel vaccine approaches, some of which have been recently and successfully employed for SARS-CoV-2 vaccines. Finally, some ideas will be presented on which methods to explore for the design of live-attenuated vaccines against HCV.

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Taming a beast: lessons from the domestication of hepatitis C virus

Cited by 10 publications

References 98 publications

Reporter Replicons for Antiviral Drug Discovery against Positive Single-Stranded RNA Viruses

Reporter Replicons for Antiviral Drug Discovery against Positive Single-Stranded RNA Viruses

Viral hepatitis update: Progress and perspectives

In the era of rapid mRNA-based vaccines: Why is there no effective hepatitis C virus vaccine yet?

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