Rapid sequence variation of the hypervariable region of hepatitis C virus during the course of chronic infection

Kurosaki, Masayuki; Enomoto, Nobuyuki; Marumo, Fumiaki; Sato, Mitsuru

doi:10.1002/hep.1840180602

Cited by 133 publications

(55 citation statements)

References 29 publications

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“…The HCV genome in single hosts is described as a dynamic population of different but closely related genomes designated quasispecies (Martell et al, 1992;Duarte et al, 1994;Domingo et al, 1998;Afonso et al, 1999). This quasispecies composition undergoes extensive variations during the course of chronic infection (Okamoto et al, 1992;Kurosaki et al, 1993;Farci et al, 1997;Afonso et al, 1999), which may result from the accumulation of random substitutions or from changes in the predominant quasispecies population under the selective pressure of the immune response (Lu et al, 2001). The HCV hypervariable region 1 (HVR1) is a 27 amino acid sequence located at the N terminus of glycoprotein E2 (Hijikata et al, 1991;Weiner et al, 1991;Kurosaki et al, 1993).…”

Section: Introductionmentioning

confidence: 99%

“…This quasispecies composition undergoes extensive variations during the course of chronic infection (Okamoto et al, 1992;Kurosaki et al, 1993;Farci et al, 1997;Afonso et al, 1999), which may result from the accumulation of random substitutions or from changes in the predominant quasispecies population under the selective pressure of the immune response (Lu et al, 2001). The HCV hypervariable region 1 (HVR1) is a 27 amino acid sequence located at the N terminus of glycoprotein E2 (Hijikata et al, 1991;Weiner et al, 1991;Kurosaki et al, 1993). HVR displays marked sequence variability, possibly corresponding to the emergence of immune escape mutants (Hijikata et al, 1991;Weiner et al, 1992;Kurosaki et al, 1993;Van Doorn et al, 1995;McAllister et al, 1998).…”

Section: Introductionmentioning

confidence: 99%

“…The HCV hypervariable region 1 (HVR1) is a 27 amino acid sequence located at the N terminus of glycoprotein E2 (Hijikata et al, 1991;Weiner et al, 1991;Kurosaki et al, 1993). HVR displays marked sequence variability, possibly corresponding to the emergence of immune escape mutants (Hijikata et al, 1991;Weiner et al, 1992;Kurosaki et al, 1993;Van Doorn et al, 1995;McAllister et al, 1998). In spite of the high variability of this region, there is a strong negative selection against some amino acid substitutions since at most codons there is selection for conservative amino acid replacement, pointing to a biological role in the virus life-cycle (McAllister et al, 1998;Sobolev et al, 2000;Penin et al, 2001).…”

Section: Introductionmentioning

confidence: 99%

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Evolutionary study of HVR1 of E2 in chronic hepatitis C virus infection

Alfonso

Flichman

Sookoian

et al. 2004

Journal of General Virology

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Hypervariable region 1 (HVR1) of the hepatitis C virus (HCV) genome was directly sequenced from 12 chronically infected patients who had not responded to interferon (IFN) treatment. Due to the quasispecies nature of HCV circulating genomes, serum samples from four patients showing different evolutionary characteristics were further analysed. Serial samples from each patient were taken before, soon after and 14-23 months after a 6 month IFN treatment. HVR1 from each sample was amplified, cloned and the clones sequenced. For each patient, a phylogenetic analysis of the clones was performed and quasispecies complexity and genetic distances were calculated. The amino acid sequences and predicted antigenic profiles were analysed. The pre-treatment samples of the different patients presented dissimilar genetic quasispecies composition. For three of the patients, we showed that, regardless of the complexity or diversity of the viral populations before treatment, they evolved towards genetic diversification following selective pressure. Once the environment became stable, the entire population tended towards homogeneity. The fourth patient represented a case where different components of the quasispecies coexisted for long periods without replacement. We propose herein that the evolution of HVR1 of E2 is more likely to be directed by selection of clearly different subpopulations (modification of quasispecies equilibrium) than by a continuous mechanism related to the successive accumulation of point mutations. The prevalence of a quasispecies shift mechanism was revealed by the cloning analysis during the follow-up period of the evolutionary process.

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Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Evolutionary study of HVR1 of E2 in chronic hepatitis C virus infection

Alfonso

Flichman

Sookoian

et al. 2004

Journal of General Virology

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“…16,17 Although this quasispecies nature of HCV is generated by the limited fidelity of RNA replication, host immunity, especially the humoral immune response, is thought to be one of the important driving forces in the sequence variations of the HVR of HCV. [18][19][20] We therefore compared the complexity of HVR 1 quasispecies of the HCV genome in serum, PBMCs, and liver to assess the pathogenic implication of HCV infection in PBMCs.…”

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confidence: 99%

Differences in Hypervariable Region 1 Quasispecies of Hepatitis C Virus in Human Serum, Peripheral Blood Mononuclear Cells, and Liver

et al. 1999

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Hepatitis C virus (HCV) has been reported to potentially replicate in peripheral blood mononuclear cells (PBMCs), but direct information on the pathogenic implication of HCV infection in PBMCs is still limited. To investigate this issue, we compared the complexity of HCV quasispecies in serum, PBMCs, and livers of 13 patients with type C chronic liver disease. Hypervariable region 1 (HVR 1) was amplified by reverse-transcription polymerase chain reaction (RT-PCR), and the PCR products were subcloned and sequenced. Considerable differences in the complexity of HVR 1 quasispecies were found in the serum, PBMCs, and liver in all patients, and the predominant sequences from each source were mutually different in 3 (23%) patients. An amino acid sequence unique to each source existed as well as a sequence common to serum and PBMCs, common to serum and livers, or common to PBMCs and liver. These results suggest infection of PBMCs by HCV, and that HCV in PBMCs may be differently exposed to host immunity from that in liver. (HEPATOLOGY 1999;29:217-222.)Hepatitis C virus (HCV), a positive-strand RNA virus, is assumed to replicate via the production of a complementary negative-strand template, like that of the closely related flaviviruses. 1,2 Several lines of evidence suggest that this virus can also infect peripheral blood mononuclear cells (PBMCs) in persistently infected individuals on the basis of specific detection of negative-strand HCV RNA in PBMCs by reversetranscription polymerase chain reaction (RT-PCR) and in situ hybridization 3-7 ; however, this issue is still controversial. [8][9][10]

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“…SSCP analysis can fail to detect minor variants, i.e. sequences representing 5 % or less of the genomic population (Kurosaki et al, 1993). Failure to demonstrate a variant in plasma may therefore reflect a quantitative or a qualitative difference.…”

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confidence: 99%

Differences in hepatitis C virus quasispecies composition between liver, peripheral blood mononuclear cells and plasma.

Maggi

Fornai

Vatteroni

et al. 1997

Journal of General Virology

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Hepatitis C virus (HCV) exists in vivo as a highly variable mixture of closely related genomes (quasispecies), but the pathogenetic significance of such heterogeneity is still largely unknown. To investigate this issue, we compared the composition of HCV quasispecies found in the liver, peripheral blood mononuclear cells (PBMC) and plasma of ten patients by single-strand conformation polymorphism analysis of the E2/NS1 region and sequencing of the variants detected. We found considerable quasispecies differences between the liver and PBMC in all the patients, involving variant numbers, relative quantities and relative electrophoretic mobilities, but no apparent tissue-specific trend. Genome variants present in the liver and/or PBMC were not detected in the corresponding plasma samples, while certain HCV variants were present only in plasma. No dominant amino acids or amino acid pattern characteristic of variants present solely in the PBMC were detected in the E2/NS1 region sequenced.Hepatitis C virus (HCV) exists within infected hosts as a variably complex system of related genomes (quasispecies) generated by the limited fidelity of RNA replication. Recent evidence has shown that quasispecies composition exhibits extensive variation within individual isolates (Okada et al., 1992) and can vary spontaneously both over time (Kao et al., 1995) and with liver disease progression . In addition, the extent of HCV quasispecies diversity has been reported to be predictive of responsiveness to interferon treatment (Moribe et al., 1995) and to decrease markedly

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Rapid sequence variation of the hypervariable region of hepatitis C virus during the course of chronic infection

Cited by 133 publications

References 29 publications

Evolutionary study of HVR1 of E2 in chronic hepatitis C virus infection

Evolutionary study of HVR1 of E2 in chronic hepatitis C virus infection

Differences in Hypervariable Region 1 Quasispecies of Hepatitis C Virus in Human Serum, Peripheral Blood Mononuclear Cells, and Liver

Differences in hepatitis C virus quasispecies composition between liver, peripheral blood mononuclear cells and plasma.

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