High amino acid variability within the NS5A of hepatitis C virus (HCV) is associated with hepatocellular carcinoma in patients with HCV-1b–related cirrhosis

Giménez‐Barcons, Mireia; Franco, Sandra; Suárez, Yanette; Forns, Xavier; Ampurdanès, Sergi; Puig-Basagoiti, Francesc; Sánchez‐Fueyo, Alberto; Barrera, Josep-Maria; Llovet, Josep M.; Bruix, Jordi; Sánchez-Tapias, José-Marı́a; Rodés, Juan; Saiz, Juan-Carlos

doi:10.1053/jhep.2001.25512

Cited by 43 publications

(45 citation statements)

References 71 publications

(110 reference statements)

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“…The genetic distance between these 10 isolates was similar to that previously documented among viral isolates in other instances of HCV transmission through different mechanisms, such as colonoscopy (4), mother to infant (20,31), and others (19,28,29). In contrast, the genetic distance between virus from the remaining two cases was much greater and similar to that previously described among epidemiologically unrelated strains from the same geographical area (9,24,25,27), suggesting that these individuals were not involved in the epidemic outbreak under consideration. Close genetic relatedness of these 10 isolates was confirmed by phylogenetic analysis, since all of them clustered together with high bootstrap values and were clearly separated from the remaining samples analyzed (Fig.…”

supporting

confidence: 85%

Outbreak of Nosocomial Hepatitis C Virus Infection Resolved by Genetic Analysis of HCV RNA

Bruguera¹,

Saiz²,

Franco³

et al. 2002

J Clin Microbiol

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In July 2000, symptomatic acute hepatitis C was diagnosed in five patients who had attended the emergency room of a municipal hospital on the same day, about 6 weeks before. Investigation of the remaining 65 patients visited at the emergency room on that day disclosed that 8 patients had a positive anti-hepatitis C virus (anti-HCV) test and 4 of them had biochemical evidence of acute anicteric hepatitis. HCV RNA was detected in 12 of the 13 anti-HCV-positive patients. Phylogenetic analysis of the nonstructural 5A (NS5A) and E2 regions showed that 10 patients, including all 9 with acute hepatitis, were infected with a closely related HCV strain, while the remaining 2 patients harbored unrelated strains. Flushing of intravenous catheters with heparin retrieved from a multidose heparin solution in saline was carried out for all the patients involved in the hepatitis outbreak but in only 1 of 23 (4%) matched controls recruited among HCV-noninfected patients attending the emergency room on the same day, and this was the only significant difference concerning risk factors for HCV infection between patients and controls. Thus, accidental contamination of a multidose heparin solution with blood from an unrecognized HCV carrier was identified as the source of this nosocomial outbreak of hepatitis C.

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supporting

confidence: 85%

Outbreak of Nosocomial Hepatitis C Virus Infection Resolved by Genetic Analysis of HCV RNA

Bruguera¹,

Saiz²,

Franco³

et al. 2002

J Clin Microbiol

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“…This region has a particular importance since previous work by Enomoto et al [148] (1995) suggested that the genetic heterogeneity of the interferon sensitivity determining region domain of HCV NS5A (IFN sensitivity-determining region), linked to response to therapy in Japanese patients [148] . Although there seems not to be a consensus on this issue [85] , the published information supports the hypothesis that an association indeed exists between NS5A and response to therapy [149][150][151] . Some reports suggest that HCV NS5A protein can act in vivo repressing PKR function, and presumably allowing HCV to escape the antiviral effects of interferon [1,3,152,153] .…”

Section: Recombinationmentioning

confidence: 88%

Hepatitis C virus genetic variability and evolution

Echeverría

Moratorio

Cristina

et al. 2015

WJH

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Hepatitis C virus (HCV) has infected over 170 million people worldwide and creates a huge disease burden due to chronic, progressive liver disease. HCV is a singlestranded, positive sense, RNA virus, member of the Flaviviridae family. The high error rate of RNA-dependent RNA polymerase and the pressure exerted by the host immune system, has driven the evolution of HCV into 7 different genotypes and more than 67 subtypes. HCV evolves by means of different mechanisms of genetic variation. On the one hand, its high mutation rates generate the production of a large number of different but closely related viral variants during infection, usually referred to as a quasispecies. The great quasispecies variability of HCV has also therapeutic implications since the continuous generation and selection of resistant or fitter variants within the quasispecies spectrum might allow viruses to escape control by antiviral drugs. On the other hand HCV exploits recombination to ensure its survival. This enormous viral diversity together with some host factors has made it difficult to control viral dispersal. Current treatment options involve pegylated interferon-α and ribavirin as dual therapy or in combination with a direct-acting antiviral drug, depending on the country. Despite all the efforts put into antiviral therapy studies, eradication of the virus or the development of a preventive vaccine has been unsuccessful so far. This review focuses on current available data reported to date on the genetic mechanisms driving the molecular evolution of HCV populations and its relation with the antiviral therapies designed to control HCV infection. Hepatitis C virus genetic variability and evolution no preventive vaccine, and though antiviral therapy has been improved in the past few years, not all patients eradicate the virus as a result of it. The main reason lies in the intrinsic genetic variability that characterises RNA viruses, such as HCV, whose RNA polymerase lacks proof-reading activity, leading to a high mutation rate and the generation of a wide range of genome variants better known as a quasispecies. Therefore this review summarises current data on HCV quasispecies dynamics, antiviral therapy and recombination events.Echeverría N, Moratorio G, Cristina J, Moreno P. Hepatitis C virus genetic variability and evolution. World J Hepatol 2015; 7(6): 831845 Available from:

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“…HCV-RNA was extracted from serum by the Trizol method following the instructions of the manufacturer (Invitrogen). Specific amplification of HCV-RNA was carried out with primers described previously (Gimenez-Barcons et al, 2001) as follows: cDNA was synthesized from viral RNA using 1?5 mM reverse primer HV2 and 0?45 U AMV reverse transcriptase ml 21 in 20 ml final volume. Ten microlitres of this cDNA was used as a template for PCR amplification using the forward primer HV1 and the reverse primer HV2 at 0?5 mM each, in a final volume of 50 ml.…”

Section: Methodsmentioning

confidence: 99%

Hepatitis C virus population analysis of a single-source nosocomial outbreak reveals an inverse correlation between viral load and quasispecies complexity

Más

Ulloa

Bruguera³

et al. 2004

Journal of General Virology

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The features of Hepatitis C virus (HCV) quasispecies within an envelope segment including the hypervariable region 1 were analysed at an early time point post-infection in seven patients that acquired HCV from a single common donor during a nosocomial outbreak. The grouping of patients according to viral load was reflected in the structure of the quasispecies. A higher viral load correlated with the presence of a predominant HCV genome and a corresponding lower quasispecies complexity. The quasispecies complexity itself was not correlated with HCV clearance or persistence. Thus, the relationship between an intrapatient HCV quasispecies and the clinical outcome of an HCV infection is more complex than previously anticipated. INTRODUCTIONHepatitis C virus (HCV) is an enveloped positive-strand RNA virus of the family Flaviviridae. Only about 15-30 % of HCV infections are spontaneously cleared, the remaining result in virus persistence with subsequent development of chronic hepatitis, liver cirrhosis and hepatocellular carcinoma (Alter et al., 1999). Because worldwide over 170 million people are infected carriers, HCV is a major health problem and a key issue in antiviral research.The mechanisms responsible for the high rate of viral persistence are thought to be the result of a complex host-virus interaction early after infection (Racanelli & Rehermann, 2003). However, little is known about these early virus and host determinants because the acute phase of infection is often asymptomatic and thus most diagnoses are made during the chronic stage, i.e. months or years after the events that determined the clinical course of the infection. While HCV induces strong humoral and cellular immune responses, their roles in virus clearance or persistence have not been fully elucidated. Studies in humans and chimpanzees indicate that a robust intrahepatic CD4 + and CD8 + T-cell response during the first weeks after infection is associated with viral clearance (Cooper et al., 1999;Major et al., 2004;Thimme et al., 2002). Also, antibodies may play a role here because an early antibody recognition of the hypervariable region 1 (HVR1) in the envelope E2 protein was correlated with virus clearance (Allander et al., 1997), and infection of chimpanzees could be inhibited by a human hyperimmune serum against HVR1 (Farci et al., 1996). In line with this are studies on the rate of HVR1 evolution that have suggested that the HVR1 region is under immune pressure exerted by neutralizing antibodies (Booth et al., 1998;Kato et al., 1993; Shimizu et al., 1994;Weiner et al., 1992). Nevertheless, by using infectious retroviral pseudotypes, a recent study has shown that neutralizing antibody responses early after infection do not seem to play a role in the resolution of an acute infection (Logvinoff et al., 2004 aspect is that HCV seems to have a wide cell tropism and can infect not only hepatocytes but also cells of the immune system (Bain et al., 2001;Sung et al., 2003). Another important feature is that HCV behaves in infected patients as a c...

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High amino acid variability within the NS5A of hepatitis C virus (HCV) is associated with hepatocellular carcinoma in patients with HCV-1b–related cirrhosis

Abstract: Hepatitis C virus (HCV) is an enveloped, single-stranded RNA virus that belongs to the Flaviviridae family.

Cited by 43 publications

References 71 publications

Outbreak of Nosocomial Hepatitis C Virus Infection Resolved by Genetic Analysis of HCV RNA

Outbreak of Nosocomial Hepatitis C Virus Infection Resolved by Genetic Analysis of HCV RNA

Hepatitis C virus genetic variability and evolution

Hepatitis C virus population analysis of a single-source nosocomial outbreak reveals an inverse correlation between viral load and quasispecies complexity

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