Hepatitis C virus shares amino acid sequence similarity with pestiviruses and flaviviruses as well as members of two plant virus supergroups.

Miller, R.H.; Purcell, Robert H.

doi:10.1073/pnas.87.6.2057

Cited by 576 publications

(340 citation statements)

References 36 publications

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“…A single open reading frame encodes a precursor polyprotein of 3010/3011 amino acids. These characteristics as well as the genomic organization and sequence homologies suggest that HCV is related to flavi-and pestiviruses (Miller & Purcell, 1990). The virus is now classified in its own genus within the flaviviridae family (Wengler, 1991).…”

Section: Introductionmentioning

confidence: 99%

Peripheral blood leukocytes serve as a possible extrahepatic site for hepatitis C virus replication

Müller

Pfaff

Goeser

et al. 1993

Journal of General Virology

229

131

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To study possible extrahepatic sites for the replication of hepatitis C virus (HCV), we examined fresh and cultured peripheral blood mononuclear lenkocytes (PBML), as well as different subpopulations of PBML of HCVinfected patients, for the presence of viral genomic and antigenomic RNA. Sense and antisense oligonucleotide primers derived from HCV sequences were used for reverse transcription (RT) followed by an amplification with the polymerase chain reaction assay (PCR). Using antisense primers for RT, genomic viral RNA could be detected in serum, liver, total PBML and B lymphocytes of chronically infected patients. However, only liver tissue and PBML specimens were positive when a sense primer was used. To demonstrate further the specificity of these findings, total PBML were stimulated using pokeweed mitogen and synthesis of HCV RNA was determined by incorporation of [3H]uridine into nascent viral RNA molecules using a hybrid release assay.

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Section: Introductionmentioning

confidence: 99%

Peripheral blood leukocytes serve as a possible extrahepatic site for hepatitis C virus replication

Müller

Pfaff

Goeser

et al. 1993

Journal of General Virology

229

131

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“…Hepatitis C virus (HCV) is an enveloped, positive-sense, single-stranded RNA virus belonging to the Hepacivirus genus of the Flaviviridae family [1]. HCV infection is one of the major reasons for chronic liver diseases and if not treated on time, often leads to liver cirrhosis and hepatocellular carcinoma.…”

Section: Introductionmentioning

confidence: 99%

Baseline dasabuvir resistance in Hepatitis C virus from the genotypes 1, 2 and 3 and modeling of the NS5B-dasabuvir complex by thein silicoapproach

Akaberi

Bergfors

Kjellin

et al. 2018

Infection Ecology & Epidemiology

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Background: Current combination treatments with direct-acting antiviral agents (DAAs) can cure more than 95% of hepatitis C virus (HCV) infections. However, resistance-associated substitutions (RASs) may emerge and can also be present in treatment-naïve patients. Methods, results and discussion: In this study, a semi-pan-genotypic population sequencing method was developed and used to assess all NS5B amino acid variants between residue positions 310 and 564. Our method successfully sequenced more than 90% of genotype (GT) 1a, 1b, 2b and 3a samples. By using the population sequencing method with a cut-off of 20%, we found the dasabuvir RASs A553V and C445F to be a baseline polymorphism of GT 2b (8 out of 8) and GT 3a (18 out of 18) sequences, respectively. In GT 1a and 1b treatment-naïve subjects (n=25), no high-fold resistance polymorphism/RASs were identified. We further predicted dasabuvir’s binding pose with the NS5B polymerase using the in silico methods to elucidate the reasons associated with the resistance of clinically relevant RASs. Dasabuvir was docked at the palm-I site and was found to form hydrogen bonds with the residues S288, I447, Y448, N291 and D318. The RAS positions 316, 414, 448, 553 and 556 were found to constitute the dasabuvir binding pocket.

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“…The levels of cytokines such as IFN-γ, TNF-α, IL-6 and IL-8 are elevated in individuals with chronic hepatitis C [74][75][76][77][78][79][80][81][82], and some authors have shown that this increase is proportional to the extent of the damage, histologically [26,76,83,84].…”

Section: Cell Response To Hcvmentioning

confidence: 99%

“…There is some evidence of direct cytopathic lesion caused by HCV, including HCV-induced histological lesions with scant inflammatory infiltrate [26][27][28], fulminant hepatitis C after chemotherapy in liver transplants [29] and HCV-related acute cholestatic syndrome after renal transplantation [30].…”

Section: Life Cycle and Pathogenicity Of Hcvmentioning

confidence: 99%

Pathogenesis of hepatitis C: HCV consensus 2007

Viso¹

2007

Braz J Infect Dis

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The chronic hepatitis C virus (HCV) infects approximately 130 million people worldwide [1]. It is estimated that approximately 15% of HCV-infected individuals eliminate the virus spontaneously, that 25% develop a mild form of the disease, and that 60% develop the chronic progressive form [2]. The elimination or persistence of HCV infection depends on the balance between the effectiveness, specificity and rapidity of the innate and adaptive immune responses, as well as on the HCV replication rate [3]. Persistence of HCV can also be caused by infection at privileged (extrahepatic) sites, viral inhibition of antigen presentation, selective immune suppression, negative regulation of HCV gene expression, viral mutations, immune exhaustion of T cells and the incomplete differentiation of memory T cells [4,5].Fibrosis is the principal complication of chronic hepatitis C, and it is estimated that 20% of patients develop cirrhosis over a period of 10, 20 or 30 years [2,6]. The progression of fibrosis increases morbidity and mortality in chronic hepatitis C [7], since it can lead to death due to complications caused by cirrhosis or hepatocarcinoma [2].Various studies have associated the progression of fibrosis in hepatitis C with diverse factors such as: the kinetics and pathogenicity of HCV; host-HCV interaction; intrinsic host factors such as demographic profile, body mass index and diabetes mellitus; host exposure to external factors; and the form of HCV acquisition. Life Cycle and Pathogenicity of HCVBelonging to the Flaviviridae family, HCV is a small enveloped virus [8]. Its genome consists of one RNA molecule that is composed of two terminal regions, 5'-and 3'-untranslated regions, and between these there is a single open reading frame that encodes a polyprotein with approximately 3000 amino acids. This polyprotein cleaves at the N-terminal side of three structural proteins, the nucleocapsid (core), envelope 1 (E1) and envelope 2 (E2), all of which are involved in the architectural organization of HCV. At the carboxylterminal side, the polyprotein cleaves to six nonstructural proteins, NS2, NS3, NS4 (NS4A and NS4B), NS5 (NS5A and NS5B) and NS6, which are responsible for the life cycle of the virus [9].After entering a susceptible host, HCV invades, infects and replicates within the blood stream, repeating the process in various tissues, as well as in peripheral B and T lymphocytes, as it proceeds to the liver by tropism, passing through various tissues such as those of the pancreas, thyroid, adrenal glands, spleen and bone marrow [10][11][12]. Since HCV can also directly infect the lymphatic tissue, its stimulation can lead to the development of B-cell lymphomas [13]. It is known that the liver is the principal site of HCV replication, and various studies have shown that this virus infects approximately 10% of hepatic cells [5]. Infection with HCV at extrahepatic sites can promote the appearance of HCV variants [14,15], thereby decreasing the chance that the immune system will recognize the virus.To enter the host ...

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Hepatitis C virus shares amino acid sequence similarity with pestiviruses and flaviviruses as well as members of two plant virus supergroups.

Abstract: Hepatitis C virus (HCV) is an important human pathogen that is associated with transfusion-related non-A, non-B hepatitis. Recently, HCV cDNA was cloned and the nudeotide sequence of approximately three-quarters of the virus genome was determined. A region of the predicted

Cited by 576 publications

References 36 publications

Peripheral blood leukocytes serve as a possible extrahepatic site for hepatitis C virus replication

Peripheral blood leukocytes serve as a possible extrahepatic site for hepatitis C virus replication

Baseline dasabuvir resistance in Hepatitis C virus from the genotypes 1, 2 and 3 and modeling of the NS5B-dasabuvir complex by thein silicoapproach

Pathogenesis of hepatitis C: HCV consensus 2007

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