Low level or absent in vivo replication of hepatitis C virus and hepatitis G virus/GB virus C in peripheral blood mononuclear cells.

Mellor, Janet; Haydon, Geoffrey; Blair, C S; Livingstone, Wendy; Simmonds, Peter

doi:10.1099/0022-1317-79-4-705

Cited by 109 publications

(99 citation statements)

References 42 publications

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“…Although several early studies found HPgV RNA in liver biopsies, virus was subsequently detected in spleen, bone marrow, cerebrospinal fluid and PBMCs, as noted above (Chivero et al, 2014;George et al, 2006; Kisiel et al, 2013;Mellor et al, 1998;Pessoa et al, 1998;Radkowski et al, 2000;Tucker et al, 2000). Studies attempting to find evidence of HPgV replication in liver tissue were either negative or inconclusive (Berg et al, 1999;Fan et al, 1999;Laskus et al, 1997).…”

Section: Hpgv Tropismmentioning

confidence: 97%

Tropism of human pegivirus (formerly known as GB virus C/hepatitis G virus) and host immunomodulation: insights into a highly successful viral infection

Chivero

Stapleton

2015

Journal of General Virology

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Human pegivirus (HPgV; originally called GB virus C/hepatitis G virus) is an RNA virus within the genus Pegivirus of the family Flaviviridae that commonly causes persistent infection. Worldwide, 750 million people are actively infected (viraemic) and an estimated 0.75-1.5 billion people have evidence of prior HPgV infection. No causal association between HPgV and disease has been identified; however, several studies described a beneficial relationship between persistent HPgV infection and survival in individuals infected with human immunodeficiency virus. The beneficial effect appeared to be related to a reduction in host immune activation. HPgV replicates well in vivo (mean plasma viral loads typically .1¾10 7 genome copies ml -1 ); however, the virus grows poorly in vitro and systems to study this virus are limited. Consequently, mechanisms of viral persistence and host immune modulation remain poorly characterized, and the primary permissive cell type (s) has not yet been identified. HPgV RNA is found in liver, spleen, bone marrow and PBMCs, including Tand B-lymphocytes, NK-cells, and monocytes, although the mechanism of cell-to-cell transmission is unclear. HPgV RNA is also present in serum microvesicles with properties of exosomes. These microvesicles are able to transmit viral RNA to PBMCs in vitro, resulting in productive infection. This review summarizes existing data on HPgV cellular tropism and the effect of HPgV on immune activation in various PBMCs, and discusses how this may influence viral persistence. We conclude that an increased understanding of HPgV replication and immune modulation may provide insights into persistent RNA viral infection of humans. IntroductionHuman pegivirus (HPgV) is an RNA virus within the Pegivirus A species and family Flaviviridae (Adams et al., 2013;Stapleton et al., 2012a). The virus was originally called hepatitis G virus (HGV)/GB virus type C (GBV-C). The letters 'GB' represented the initials of a surgeon with acute hepatitis whose sera caused hepatitis in marmosets (Deinhardt et al., 1967). Subsequent studies found that this virus did not cause hepatitis and there was no direct evidence that the surgeon ('G. B.') was infected with HPgV. Thus, the virus (HGV/GBV-C), along with several related primate and bat viruses (GBV-A, GBV-C czp , GBV-D), was assigned to a new genus (Pegivirus) and renamed as HPgV (Adams et al., 2013;Stapleton et al., 2012a). HPgV has a 9.4 kb positive-sense ssRNA genome that is organized similarly to hepatitis C virus (HCV) (Fig. 1). HPgV and HCV are unusual amongst RNA viruses in that they commonly cause persistent infection in immune-competent humans.Although HPgV is not as efficient at establishing persistent infection as HCV, an estimated 25 % of infections persist and the other 75 % clear viraemia within 2 years of infection (Gutierrez et al., 1997;Tanaka et al., 1998a). The prevalence of HPgV viraemia in cross-sectional serum surveys of healthy blood donors in developed countries is between 1 and 5 %, whilst up to 20 % of blood donors in ...

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Section: Hpgv Tropismmentioning

confidence: 97%

Tropism of human pegivirus (formerly known as GB virus C/hepatitis G virus) and host immunomodulation: insights into a highly successful viral infection

Chivero

Stapleton

2015

Journal of General Virology

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“…HCV transcripts have been observed at low levels in DCs and other lymphoid cells (35,36) but these do not seem to represent significant reservoirs of HCV. However, L-SIGN and DC-SIGN interactions may contribute to immune dysregulation, including the impaired DC function observed in chronic HCV infection (37)(38)(39).…”

Section: Discussionmentioning

confidence: 99%

L-SIGN (CD 209L) is a liver-specific capture receptor for hepatitis C virus

Gardner

Durso

Arrigale

et al. 2003

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

262

221

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“…This possibility is supported by the demonstration of HCV replication in hematopoietic cells inoculated into severe combined immunodeficiency mice. 16 Moreover, whereas HCV RNA-negative strand rarely is detected in peripheral-blood mononuclear cells from healthy subjects, 17,18 it commonly is found in HIV-coinfected patients or liver transplant recipients. 9,19 We speculate that HCV infection of the CNS may provide the biological substrate for neuropsychiatric syndromes associated with this viral infection.…”

Section: Discussionmentioning

confidence: 99%

Detection of hepatitis C virus sequences in brain tissue obtained in recurrent hepatitis C after liver transplantation

et al. 2002

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Patients with chronic hepatitis C frequently report tiredness, easy fatigability, and depression. The aim of this study is to determine whether hepatitis C virus (HCV) replication could be found in brain tissue in patients with hepatitis C and depression. We report two patients with recurrent hepatitis C after liver transplantation who also developed severe depression. One patient died of multiorgan failure and the other, septicemia caused by Staphylococcus aureus. Both patients had evidence of severe hepatitis C recurrence with features of cholestatic fibrosing hepatitis. We were able to study samples of their central nervous system obtained at autopsy for evidence of HCV replication. The presence of HCV RNA-negative strand, which is the viral replicative form, was determined by strand-specific Tth-based reverse-transcriptase polymerase chain reaction. Viral sequences were compared by means of single-strand conformation polymorphism and direct sequencing. HCV RNA-negative strands were found in subcortical white matter from one patient and cerebral cortex from the other patient. HCV RNA-negative strands amplified from brain tissue differed by several nucleotide substitutions from serum consensus sequences in the 5 untranslated region. These findings support the concept of HCV neuroinvasion, and we speculate that it may provide a biological substrate to neuropsychiatric disorders observed in patients with chronic hepatitis C. P atients with chronic hepatitis C frequently report tiredness, easy fatigability, and depression. Dwight et al 1 reported that 28% of patients with chronic hepatitis C had current depressive disorders. They concluded that disability and fatigue were related more closely to severity of depression than to progression of liver disease. More recently, Forton et al 2 addressed the hypothesis that hepatitis C virus (HCV) itself may affect cerebral function and provide the substrate for the chronic fatigue syndrome frequently associated with HCV infection. The investigators used proton magnetic resonance spectroscopy and showed elevations in choline-creatine ratios in the basal ganglia and white matter of patients with histologically mild hepatitis C that were not present in healthy volunteers and patients with hepatitis B. This elevated ratio was unrelated to hepatic encephalopathy or a history of intravenous drug abuse. The investigators suggested that a biological process underlies extrahepatic symptoms in chronic HCV infection, although they did not speculate on its nature. Furthermore, because HCV has been found to replicate in lymphoid cells and monocyte/ macrophages 3-5 and these cells can enter the central nervous system (CNS), 6 a possibility remains that psychosomatic syndromes observed in patients with HCV infection are related to viral replication in the CNS.We studied two patients with recurrent hepatitis C after cadaveric liver transplantation for end-stage liver disease caused by HCV infection who presented a clinical picture of profound depression. These patients subsequently died,...

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Low level or absent in vivo replication of hepatitis C virus and hepatitis G virus/GB virus C in peripheral blood mononuclear cells.

Cited by 109 publications

References 42 publications

Tropism of human pegivirus (formerly known as GB virus C/hepatitis G virus) and host immunomodulation: insights into a highly successful viral infection

Tropism of human pegivirus (formerly known as GB virus C/hepatitis G virus) and host immunomodulation: insights into a highly successful viral infection

L-SIGN (CD 209L) is a liver-specific capture receptor for hepatitis C virus

Detection of hepatitis C virus sequences in brain tissue obtained in recurrent hepatitis C after liver transplantation

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