Immune system control of hepatitis C virus infection

Stuart, Johnasha D.; Salinas, Eduardo; Grakoui, Arash

doi:10.1016/j.coviro.2020.10.002

Cited by 30 publications

(26 citation statements)

References 77 publications

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“…In recent years, several groups have investigated the recovery of the altered NK cell compartment upon successful antiviral treatment, but it is still a matter of research whether an active reinvigoration via certain signaling pathways or the resolution of inflammation after virus elimination are responsible for a seemingly restored NK cell compartment. Hence, such a persistent challenge of the immune system might trigger irreversible damage that in turn could affect the success of any therapeutic vaccine design or even any immunotherapy approach against HCC[ 94 , 103 , 111 ].…”

Section: Hcvmentioning

confidence: 99%

“…A faster and more effective viral replication control at second exposures indicates an adaptive immune response that may avoid chronic infection even though it cannot prevent reinfection. Therefore, a vaccine that induces T and B cell responses against multiple HCV genotypes and impedes the selection of virus escape mutants is needed[ 111 , 113 ]. While attenuated vaccines by the passage of the virus in non-human primate cell lines could be produced and suppress or inactivate genetic virulence factors, HCV does not replicate at high levels in non-human primate cell lines and no virulence factors have been defined for HCV yet.…”

Section: Hcvmentioning

confidence: 99%

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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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Section: Hcvmentioning

confidence: 99%

Section: Hcvmentioning

confidence: 99%

Viral hepatitis update: Progress and perspectives

Pisano¹,

Giadans²,

Flichman³

et al. 2021

WJG

View full text Add to dashboard Cite

show abstract

“…Despite immune activation, HCV can often evade the host response and establish persistent infection [46]. There is a consensus regarding the defective and not maintained adaptive immunity present in patients that progress to CHC [47]. The main challenge to developing an effective preventive HCV vaccine is that HCV does not elicit protection against reinfection.…”

Section: Hcv Therapymentioning

confidence: 99%

“…However, in most cases, re-challenged animals have exhibited protection against developing CHC, indicating some degree of protective immunity [49]. Similarly, CHC patients who exhibit viremia resolution following antiviral therapy do not acquire protective immunity, and can thus experience reinfection [47]. Reinfections can even occur with the same HCV subtype [50], suggesting the difficulty of designing a prophylactic HCV vaccine.…”

Section: Hcv Therapymentioning

confidence: 99%

“…The absence of data about the immunological determinants of viral clearance, persistence and protective immunity is a major barrier to the development of a prophylactic HCV vaccine [47]. Recent work has shown that HCV variants isolated pre-seroconversion are more sensitive to the antiviral activity of first line innate immune response represented by interferon-induced transmembrane proteins than variants from patients isolated during CHC post-seroconversion [51].…”

Section: Hcv Therapymentioning

confidence: 99%

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Therapy Implications of Hepatitis C Virus Genetic Diversity

Martı́nez

Franco

2020

Viruses

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Hepatitis C virus (HCV) is an important human pathogen with a high chronicity rate. An estimated 71 million people worldwide are living with chronic hepatitis C (CHC) infection, which carries the risk of progression to hepatic fibrosis, cirrhosis, and hepatocellular carcinoma (HCC). Similar to other RNA viruses, HCV has a high rate of genetic variability generated by its high mutation rate and the actions of evolutionary forces over time. There are two levels of HCV genetic variability: intra-host variability, characterized by the distribution of HCV mutant genomes present in an infected individual, and inter-host variability, represented by the globally circulating viruses that give rise to different HCV genotypes and subtypes. HCV genetic diversity has important implications for virus persistence, pathogenesis, immune responses, transmission, and the development of successful vaccines and antiviral strategies. Here we will discuss how HCV genetic heterogeneity impacts viral spread and therapeutic control.

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Imprint of unconventional T‐cell response in acute hepatitis C persists despite successful early antiviral treatment

Khera

Strunz

et al. 2021

Eur J Immunol

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Unconventional T cells (UTCs) are a heterogeneous group of T cells that typically exhibit rapid responses toward specific antigens from pathogens. Chronic hepatitis C virus (HCV) infection causes dysfunction of several subsets of UTCs. This altered phenotype and function of UTCs can persist over time even after direct‐acting antiviral (DAA)‐mediated clearance of chronic HCV. However, it is less clear if and how UTCs respond in acute, symptomatic HCV infection, a rare clinical condition, and if rapid DAA treatment of such patients reverses the caused perturbations within UTCs. Here, we comprehensively analyzed the phenotype and reinvigoration capacity of three major UTC populations, mucosal‐associated invariant T (MAIT) cells, γδ T cells, and CD4 and CD8 double‐negative αβ T cells (DNT cells) before, during, and after DAA‐mediated clearance of acute symptomatic HCV infection. Furthermore, MAIT cell functionality was systematically studied. We observed a reduced frequency of MAIT cells. However, remaining cells presented with a near‐to‐normal phenotype in acute infection, which contrasted with a significant dysfunction upon stimulation that was not restored after viral clearance. Notably, DNT and γδ T cells displayed a strong activation ex‐vivo in acute HCV infection, which subsequently normalized during the treatment. In addition, DNT cell activation was specifically associated with liver inflammation and inflammatory cytokines. Altogether, these data provide evidence that UTCs respond in a cell type‐specific manner during symptomatic HCV infection. However, even if early treatment is initiated, long‐lasting imprints within UTCs remain over time.

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Immune system control of hepatitis C virus infection

Cited by 30 publications

References 77 publications

Viral hepatitis update: Progress and perspectives

Viral hepatitis update: Progress and perspectives

Therapy Implications of Hepatitis C Virus Genetic Diversity

Imprint of unconventional T‐cell response in acute hepatitis C persists despite successful early antiviral treatment

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