Cell culture-produced hepatitis C virus does not infect peripheral blood mononuclear cells

Marukian, Svetlana; Jones, Christopher T.; Andrus, Linda; Evans, Matthew J.; Ritola, Kimberly; Charles, Edgar D.; Rice, Charles M.; Dustin, Lynn B.

doi:10.1002/hep.22550

Cited by 225 publications

(260 citation statements)

References 42 publications

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“…(30). Hepatitis C virus (Jc1FLAG2[p7-nsGluc2a]) was kindly provided by Charles Rice (Rockefeller University, New York, NY) and grown as described previously (31).…”

Section: Methodsmentioning

confidence: 99%

Broad-spectrum antiviral that interferes with de novo pyrimidine biosynthesis

Hoffmann

Kunz

Simon

et al. 2011

Proc. Natl. Acad. Sci. U.S.A.

219

206

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Compound A3 was identified in a high-throughput screen for inhibitors of influenza virus replication. It displays broad-spectrum antiviral activity, and at noncytotoxic concentrations it is shown to inhibit the replication of negative-sense RNA viruses (influenza viruses A and B, Newcastle disease virus, and vesicular stomatitis virus), positive-sense RNA viruses (Sindbis virus, hepatitis C virus, West Nile virus, and dengue virus), DNA viruses (vaccinia virus and human adenovirus), and retroviruses (HIV). In contrast to mammalian cells, inhibition of viral replication by A3 is absent in chicken cells, which suggests species-specific activity of A3. Correspondingly, the antiviral activity of A3 can be linked to a cellular protein, dihydroorotate dehydrogenase (DHODH), which is an enzyme in the de novo pyrimidine biosynthesis pathway. Viral replication of both RNA and DNA viruses can be restored in the presence of excess uracil, which promotes pyrimidine salvage, or excess orotic acid, which is the product of DHODH in the de novo pyrimidine biosynthesis pathway. Based on these findings, it is proposed that A3 acts by depleting pyrimidine pools, which are crucial for efficient virus replication.

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“…(30). Hepatitis C virus (Jc1FLAG2[p7-nsGluc2a]) was kindly provided by Charles Rice (Rockefeller University, New York, NY) and grown as described previously (31).…”

Section: Methodsmentioning

confidence: 99%

Broad-spectrum antiviral that interferes with de novo pyrimidine biosynthesis

Hoffmann

Kunz

Simon

et al. 2011

Proc. Natl. Acad. Sci. U.S.A.

219

206

View full text Add to dashboard Cite

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“…2B, left panel). Because quantitative PCR analysis could not be performed directly on purified DCs, it is conceivable that, in some cases, we did not detect significant viral RNA inhibition (,50% inhibition) after 24 h because of the cellassociated HCV RNA decay rate [t 1/2 ∼11 h (23)]; the presence of a large (and variable) fraction of cells types in PBMCs that harbor HCV RNA in vivo but are not expected to support replication (24); and the small number of MDCs nonfunctional for cytokine (14)]. Nevertheless, consistent with the above observations, there was a positive correlation between HCV inhibition (calculated from the residual levels of HCV RNA in PBMCs at 24 h posttreatment) and increases in cytokine-expressing MDC frequencies after LPS stimulation (p = 0.0022; Fig.…”

Section: Hcv Inhibitors Can Restore Dc-mediated Innate Sensing In Cp-mentioning

confidence: 99%

Dendritic Cell Inhibition Is Connected to Exhaustion of CD8+ T Cell Polyfunctionality during Chronic Hepatitis C Virus Infection

Rodrigue-Gervais

Rigsby

Jouan

et al. 2010

The Journal of Immunology

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“…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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Cell culture-produced hepatitis C virus does not infect peripheral blood mononuclear cells

Cited by 225 publications

References 42 publications

Broad-spectrum antiviral that interferes with de novo pyrimidine biosynthesis

Broad-spectrum antiviral that interferes with de novo pyrimidine biosynthesis

Dendritic Cell Inhibition Is Connected to Exhaustion of CD8+ T Cell Polyfunctionality during Chronic Hepatitis C Virus Infection

Host–virus interactions in hepatitis B and hepatitis C infection

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