Natural killer cell function is intact after direct exposure to infectious hepatitis C virions†

Yoon, Jae-Cheol; Shiina, Masaaki; Ahlenstiel, Golo; Rehermann, Barbara

doi:10.1002/hep.22624

Cited by 94 publications

(97 citation statements)

References 37 publications

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“…Although an interesting possibility, it would not explain the low IFN-γ production during baseline. Furthermore, another study by Yoon et al [12] has recently demonstrated that exposure of NK cells from healthy donors to in vitro-produced HCV virions did not influence their function. Another possible explanation for low IFN-γ production by NK cells, in this particular cohort, is opioid abuse.…”

Section: Discussionmentioning

confidence: 97%

“…First, HCV surface glycoprotein E2 can bind CD81 on the surface of NK cells and inhibit cytotoxicity and IFN-γ production [10,11], but Yoon et al have recently demonstrated that exposure of NK cells from healthy donors to in vitro-produced HCV virions did not influence their function [12]. Second, genes encoding the inhibitory NK cell receptor killer-cell immunoglobulin like receptor (KIR)2DL3 and its human leukocyte antigen C group 1 (HLA-C1) ligand directly influence resolution of HCV infection in individuals homozygous for these genes [13,14].…”

Section: Introductionmentioning

confidence: 99%

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Increased degranulation of natural killer cells during acute HCV correlates with the magnitude of virus-specific T cell responses

Pelletier

Drouin

Bédard

et al. 2010

Journal of Hepatology

105

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Background/Aims-Natural killer (NK) cells provide early defense against viral infections by killing infected cells and producing cytokines that inhibit viral replication. NK cells also interact with dendritic cells (DCs) and this reciprocal interaction regulates both innate and adaptive immunity. Genetic studies have suggested that NK cell activity is a determinant of HCV infectious outcome but a functional correlation was not established. We hypothesized that increased NK cell activity during acute HCV infection will correlate with spontaneous viral clearance.

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Section: Discussionmentioning

confidence: 97%

Section: Introductionmentioning

confidence: 99%

Increased degranulation of natural killer cells during acute HCV correlates with the magnitude of virus-specific T cell responses

Pelletier

Drouin

Bédard

et al. 2010

Journal of Hepatology

105

View full text Add to dashboard Cite

show abstract

“…Studies involving the inoculation of cell-cultured HCV (HCVcc) into various blood cells, including DCs, have been performed in order to reveal HCV tropism [86]. However, to date no direct evidence has been obtained for the replication and reproduction of HCVcc in these cells [87][88][89], although HCVcc does have a negative impact on IFN-a production by pDCs, independently of direct infection of HCV [90]. Of particular interest, Dolguanic et al proposed a novel mechanism of third-party cells involved in pDC dysfunction.…”

Section: Dcs In Chronic Hcv Infectionmentioning

confidence: 99%

Host–virus interactions in hepatitis B and hepatitis C infection

Yoshio

Kanto

2016

J Gastroenterol

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Hepatitis B virus (HBV) and hepatitis C virus (HCV) are among the most endemic pathogens worldwide, with more than 500 million people globally currently infected with these viruses. These pathogens can cause acute and chronic hepatitis that progress to liver cirrhosis or hepatocellular carcinoma. Both viruses utilize multifaceted strategies to evade the host surveillance system and fall below the immunological radar. HBV has developed specific strategies to evade recognition by the innate immune system and is acknowledged to be a stealth virus. However, extensive research has revealed that HBV is recognized by dendritic cells (DCs) and natural killer (NK) cells. Indoleamine-2, 3-dioxygenase is an enforcer of sequential immune reactions in acute hepatitis B, and this molecule has been shown to be induced by the interaction of HBV-infected hepatocytes, DCs, and NK cells. The interleukin-28B genotype has been reported to influence HCV eradication either therapeutically or spontaneously, but the biological function of its gene product, a type-III interferon (IFN-k3), remains to be elucidated. Human BDCA3 ? DCs have also been shown to be a potent producer of IFN-k3 in HCV infection, suggesting the possibility that BDCA3 ? DCs could play a key role in developing therapeutic HCV vaccine. Here we review the current state of research on immune responses against HBV and HCV infection, with a specific focus on innate immunity. A comprehensive study based on clinical samples is urgently needed to improve our understanding of the immune mechanisms associated with viral control and thus to develop novel immune modulatory therapies to cure chronic HBV and HCV infection.

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“…Briefly, HCVcc do not stimulate NK-cell activation and IFN-c production and they do not inhibit activation, cytoxicity or IFN-c production of anti-CD16-stimulated NK cells isolated from healthy donors (Yoon et al, 2009). …”

Section: In Vitro Experimental Models: Insight Into Innate Immune Resmentioning

confidence: 99%

Experimental models to study the immunobiology of hepatitis C virus

Lohmann

Bartenschlager

et al. 2010

Journal of General Virology

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Effective host immune responses are essential for the control of hepatitis C virus (HCV) infection and persistence of HCV has indeed been attributed to their failure. In recent years, several in vitro and in vivo experimental models have allowed studies of host immune responses against HCV. Numerous observations derived from these models have improved our understanding of the mechanisms responsible for the host's ability to clear the virus as well as of the mechanisms responsible for the host's failure to control HCV replication. Importantly, several findings obtained with these model systems have been confirmed in studies of acutely or chronically HCV-infected individuals. Collectively, several mechanisms are used by HCV to escape host immune responses, such as poor induction of the innate immune response and escaping/impairing adaptive immunity. In this review, we summarize current findings from experimental models available for studies of the immune response targeting HCV and discuss the relevance of these findings for the in vivo situation in HCV-infected humans. IntroductionHepatitis C virus (HCV) is an enveloped RNA virus that belongs to the genus Hepacivirus within the family Flaviviridae. The positive-strand genome has a length of 9.6 kb and it encodes a polyprotein that is cleaved by viral and cellular proteases into 10 different proteins (reviewed by Moradpour et al., 2007). The structural proteins core, envelope protein 1 (E1) and E2 reside in the amino-terminal region of the polyprotein and they are the main constituents of infectious virus particles. The hydrophobic p7 protein together with non-structural protein 2 (NS2) are required for virion assembly. The serine-type protease residing in NS3 forms a stable complex with the NS4A cofactor and contributes to polyprotein cleavage. NS4B induces alterations of intracellular membranes, designated the membranous web, which is thought to be the site of viral RNA replication. NS5A is required for RNA replication and assembly and NS5B is the RNA-dependent RNA polymerase.HCV has a narrow host range and infects only humans and chimpanzees. It is estimated that~130 million people are persistently infected by HCV worldwide (reviewed by Shepard et al., 2005). Limited therapy options and the lack of a preventive vaccine aggravate this medical issue (reviewed by Lauer & Walker, 2001). Of note, the virus is able to establish persistence in approximately two-thirds of infected subjects and has thus become a major cause of chronic liver inflammation that can culminate in liver cirrhosis or even hepatocellular carcinoma (reviewed by Lauer & Walker, 2001). It is still not completely clear why successful immune responses allow only one-third of infected subjects to clear HCV. A major limitation when addressing this issue is the lack of an immunocompetent small animal model. Importantly, however, by using novel cell culture systems, some of these hurdles have now been overcome and first important insights into the intimate interaction between HCV and its host cell have b...

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Natural killer cell function is intact after direct exposure to infectious hepatitis C virions†

Cited by 94 publications

References 37 publications

Increased degranulation of natural killer cells during acute HCV correlates with the magnitude of virus-specific T cell responses

Increased degranulation of natural killer cells during acute HCV correlates with the magnitude of virus-specific T cell responses

Host–virus interactions in hepatitis B and hepatitis C infection

Experimental models to study the immunobiology of hepatitis C virus

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