Thank you for visiting nature.com. You are using a browser version with limited support for CSS. To obtain
the best experience, we recommend you use a more up to date browser (or turn off compatibility mode in
Internet Explorer). In the meantime, to ensure continued support, we are displaying the site without styles
and JavaScript.
This collection of research, review and comment from Nature Research celebrates the 2020 Nobel Prize in Physiology or Medicine awarded to Harvey J. Alter, Michael Houghton and Charles M. Rice "for the discovery of hepatitis C virus". Chronic viral hepatitis is a global health concern and is a major cause of cirrhosis and liver cancer. Work by the prize-winning scientists demonstrated that an unknown virus was the cause of unexplained cases of chronic hepatitis, isolated the viral genetic sequence that led to its identification as hepatitis C virus and provided the final proof that this virus alone could cause hepatitis. This work led to blood tests that improved global health and antiviral drugs that mean the disease can now be cured and perhaps one day eradicated.
To replicate in Huh7 hepatoma cells, HCV must acquire mutations that prevent PI4KA over-activation. PI4KA-specific inhibitors promote replication of unadapted viral isolates and allow replication of patient-derived virus in cell culture.
This report identifies the gap junction protein occludin as the fourth and final key component of the hepatitis C virus cell-entry receptor, paving the way towards the development of a small animal model for hepatitis C virus.
Hepatitis C virus research is hampered by the inability to detect individual infected cells. Jones et al. achieve this by imaging the translocation of a fluorescent reporter protein after cleavage by a viral protease in living or fixed cells.
Hepatitis C virus cannot replicate in cell culture unless it possesses adaptive mutations; here, expression of cellular factor SEC14L2 is shown to allow replication of diverse hepatitis C virus genotypes in several hepatoma cell lines by enhancing vitamin E-mediated protection against lipid peroxidation.
The specificity of interferon effectors across an expanded range of viruses is studied, with results indicating that positive-sense single-stranded RNA viruses are more susceptible to interferon-stimulated gene activity than negative-sense RNA or DNA viruses; in addition, the DNA sensor cGAS is shown to have an unappreciated role in RNA virus inhibition.
Hepatitis C virus (HCV) is a positive-strand RNA virus that causes significant pathology in humans. Here, Lindenbach and Rice discuss recent insights into the unique properties of HCV particles and then review HCV entry and assembly, with a focus on the viral and host factors involved.
A new wave of antivirals to fight hepatitis C infection has helped patients achieve a good quality of life, but drug resistance, side effects and a lack of pan-viral genotype coverage still remains a problem. This Review discusses current clinical studies and potential targets of the virus life cycle to tackle these issues and puts forward a paradigm to develop second-generation effective antivirals and drug combinations for achieving the ideal regimen of an all-oral, interferon-free therapeutic cocktail.
This protocol uses micropatterned co-cultures comprising 2D islands of primary human hepatocytes surrounded by supportive fibroblast cells to model liver infection by the hepatitis B and C viruses or Plasmodium pathogens in vitro.
Infection with hepatitis C is one of the main causes of liver disease, yet there are no broadly effective treatments. Discovery of a potent inhibitor of this virus shows that researchers must think outside the box.
Hepatitis C virus causes severe liver disease. Initial trials of a newly developed agent that prevents the virus reproducing itself look promising. But what are the future prospects for this treatment?
Most research prizes in biomedicine, from the Nobels to the Laskers, are restricted to three recipients. But in an age of big science, when much larger teams are generally needed to make important research discoveries, all the people who provide seminal contributions deserve to be awarded.
Viral hepatitis is a global public health problem. In this Viewpoint, we asked a selection of scientists and clinicians working in the viral hepatitis field to provide their opinions on progress and pitfalls towards the 2030 viral hepatitis elimination goals.
The World Health Organization’s targets for eliminating hepatitis C virus by 2030 have been deemed ambitious by many. However, we believe they are achievable, provided they are supported by global commitment.
Hepatitis C virus infection can cause acute and chronic hepatitis C, which are both characterized by inflammation of the liver. In this Primer, Manns et al. describe the latest developments against the global hepatitis C epidemic in the era of highly effective therapies.
Comparing the immune responses to and immunopathogenesis of infection with hepatitis A virus (HAV), hepatitis B virus (HBV) and hepatitis C virus (HCV) provides insight into the distinct outcomes of each type of viral hepatitis.
This Review describes the epidemiology and mechanisms underlying the reciprocal relationship between hepatitis C virus (HCV) infection and chronic kidney disease (CKD). The authors also discuss recommended treatment approaches for patients with HCV infection and CKD, and outline remaining issues in the field.
The past 10 years have witnessed incredible developments in the treatment of hepatitis C. From an era in which the standard of care was PEG-IFN and ribavirin back in 2004, various interferon-free regimens with direct-acting antivirals are now available or will be soon. Here, major milestones in the hepatitis C treatment revolution are outlined.
Direct-acting antiviral agents (DAAs) have revolutionized the management of chronic hepatitis C, but their use in acute infection is unclear. This Review outlines the epidemiology, diagnosis and management of acute HCV infection, providing insights into the use of DAAs in at-risk populations (such as people who inject drugs).
Chronic HCV infection is a global health problem. In this Review, the authors describe the global burden of hepatitis C and HCV-related disease, including hepatocellular carcinoma, cirrhosis and extrahepatic manifestations. How the new direct-acting antiviral agents might influence disease burden is also discussed.
Late presentation to hepatitis B virus and hepatitis C virus care is common, hindering global efforts to reduce the morbidity and mortality associated with liver disease. Models of care promoting and simplifying early testing of viral hepatitis are needed if we are to eliminate viral hepatitis as a major public health threat by 2030.
Cryoglobulinaemia is characterized by the presence of precipitable immunoglobulins in the serum and can lead to a clinical syndrome called cryoglobulinaemic vasculitis. This Primer describes the underlying mechanisms, diagnosis and management of cryoglobulinaemia.
A growing body of evidence suggests that chronic hepatitis C infection is associated with an increased rate of extrahepatic cancers. In this Review, the authors summarize epidemiological studies exploring this relationship and provide insights into the potential mechanisms underlying a causal link.
New national hepatitis C virus (HCV) screening guidance from the United States Preventive Services Task Force includes a recommendation for one-time testing for all adults aged 18 to 79 years. Implicit in the new guidance is that all people diagnosed with chronic HCV infection should be offered HCV treatment.
Almost 200 million people worldwide are chronically infected with hepatitis C virus. Current treatments are poorly tolerated and not wholly effective, so new drugs are needed. Here, a potent new inhibitor of hepatitis C virus is described. This inhibitor targets the viral protein NS5A, and shows potential as part of a therapeutic regimen based on a combination of viral inhibitors.
Preclinical studies show that fluoxazolevir, which inhibits the fusion of hepatitis C virus (HCV) with hepatic cells by binding viral envelope protein 1, could be useful in drug cocktails to treat HCV.
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.
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.
Treatment options for hepatitis C virus (HCV) infection have limited efficacy and high toxicity, resulting in poor adherence and, thus, viral resistance. Identifying previously unrecognized pathways involved in HCV infection may aid the development of new therapeutics. Using an RNAi screen, Lupberger et al. have identified cellular kinases involved in HCV infection of liver cells and have tested the ability of approved inhibitors to block viral entry both in vitro and in vivo.
Koichi Matsuda and colleagues report a genome-wide association study for hepatitis C virus–induced hepatocellular carcinoma. They identify a susceptibility locus at MICA in individuals of Japanese ancestry.