Time-Related Changes in Full-Length Hepatitis C Virus Sequences and Hepatitis Activity

Nagayama, Kazuyoshi; Kurosaki, Masayuki; Enomoto, Nobuyuki; Maekawa, Shinya; Miyasaka, Yuka; Tazawa, Junichi; Izumi, Namiki; Marumo, Fumiaki; Sato, Chifumi

doi:10.1006/viro.1999.9924

Cited by 27 publications

(32 citation statements)

References 37 publications

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“…In fact, fitness variations in constant environments have been described in other viral systems (9,42). The high rate of nucleotide changes within and between samples contrasts with the overall low rate of amino acid changes (32) so that the most heterogeneous populations had no more than five groups of sequences differing at one or two amino acid positions (Fig. 1B).…”

Section: Discussionmentioning

confidence: 74%

Longitudinal Evaluation of the Structure of Replicating and Circulating Hepatitis C Virus Quasispecies in Nonprogressive Chronic Hepatitis C Patients

Cabot

Martell

Esteban

et al. 2001

J Virol

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In previous cross-sectional studies, we demonstrated that, in most patients with chronic hepatitis C, the composition and complexity of the circulating hepatitis C virus (HCV) population do not coincide with those of the virus replicating in the liver. In the subgroup of patients with similar complexities in both compartments, the ratio of quasispecies complexity in the liver to that in serum (liver/serum complexity ratio) of paired samples correlated with disease stage. In the present study we investigated the dynamic behavior of viral population parameters in consecutive paired liver and serum samples, obtained 3 to 6 years apart, from four chronic hepatitis C patients with persistently normal transaminases and stable liver histology. We sequenced 359 clones of a genomic fragment encompassing the E2(p7)-NS2 junction, in two consecutive liver-serum sample pairs from the four patients and in four intermediate serum samples from one of the patients. The results show that the liver/serum complexity ratio is not stable but rather fluctuates widely over time. Hence, the liver/serum complexity ratio does not identify a particular group of patients but a particular state of the infecting quasispecies. Phylogenetic analysis and signature mutation patterns showed that virtually all circulating sequences originated from sequences present in the liver specimens. The overall behavior of the circulating viral quasispecies appears to originate from changes in the relative replication kinetics of the large mutant spectrum present in the infected liver.Hepatitis C virus (HCV) is one of the leading causes of chronic liver disease worldwide (22). The quasispecies nature of the single-stranded RNA genome of HCV is thought to play a central role in maintaining and modulating viral replication (10, 29). In general, the natural history of HCV infection does not follow a defined pattern, but the rates of progression of the disease (from minimal changes of the liver to cirrhosis and hepatocarcinoma) vary greatly in different individuals (22). The cytopathic potential of the virus and the characteristics of the host's immune response have both been postulated to explain the observed differences in disease progression (6,17,18,45).In the absence of an appropriate animal model or culture system and in the context of the extreme heterogeneity of HCV, it has not been possible to associate particular sequences with distinct cytopathic potential. Similarly, attempts to correlate the process of quasispecies diversification with disease progression have yielded controversial results. While in crosssectional studies some authors found a correlation between quasispecies complexity and extent of liver damage (20,20,21,25,48), others did not (19,27,33,41). In longitudinal studies, the nucleotide complexity of the hypervariable domain of the HCV E2 region (HVR1) did not increase cumulatively over time but fluctuated in consecutive serum samples (2). Similarly, at more conserved regions of the genome, an oscillatory pattern of quasispecies complexit...

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Section: Discussionmentioning

confidence: 74%

Longitudinal Evaluation of the Structure of Replicating and Circulating Hepatitis C Virus Quasispecies in Nonprogressive Chronic Hepatitis C Patients

Cabot

Martell

Esteban

et al. 2001

J Virol

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“…Briefly, RNA was extracted from the stored sera of these patients and was reverse transcribed to cDNA. Then two-step nested PCR was carried out with primers specific for the core region of the HCV genome (23). The primers for the second-round PCR had barcodes attached, were 10 nucleotides (nt) long, and differed for each sample, so that PCR products from each sample were identifiable (see Table S1 in the supplemental material).…”

Section: Patientsmentioning

confidence: 99%

Deep-Sequencing Analysis of the Association between the Quasispecies Nature of the Hepatitis C Virus Core Region and Disease Progression

Miura

Maekawa

Takano

et al. 2013

J Virol

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, and the ratio of mutant residues to R in the mixture increased as liver disease advanced to LC and HCC. Meanwhile, phylogenetic analysis of the almost-complete core region revealed that the HCV isolates differed genetically depending on the mutation status at core aa 70. We conclude that the core aa 70 mixture ratio, determined by deep sequencing, reflected the status of liver disease, demonstrating a significant association between core aa 70 and disease progression in CH patients infected with HCV genotype 1b.

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“…The nucleotide sequence is 98% identical and the amino acid sequence is 100% identical to those of HCV strain MD7-1. 30 The HCV core region was subcloned into expression vector pcDNA3 with the NH 2 -terminal Myc tag. Expression of all HCV proteins, including the core, envelope proteins (E1and E2), and nonstructural proteins (NS1, NS2, NS3, NS4A, NS4B, NS5A, and NS5B) were confirmed by immunoblotting in our previous study.…”

Section: Core and Hcv Cdnamentioning

confidence: 99%

Hepatitis C Virus Down-Regulates Insulin Receptor Substrates 1 and 2 through Up-Regulation of Suppressor of Cytokine Signaling 3

Kawaguchi¹,

Yoshida²,

Harada³

et al. 2004

The American Journal of Pathology

507

424

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Time-Related Changes in Full-Length Hepatitis C Virus Sequences and Hepatitis Activity

Cited by 27 publications

References 37 publications

Longitudinal Evaluation of the Structure of Replicating and Circulating Hepatitis C Virus Quasispecies in Nonprogressive Chronic Hepatitis C Patients

Longitudinal Evaluation of the Structure of Replicating and Circulating Hepatitis C Virus Quasispecies in Nonprogressive Chronic Hepatitis C Patients

Deep-Sequencing Analysis of the Association between the Quasispecies Nature of the Hepatitis C Virus Core Region and Disease Progression

Hepatitis C Virus Down-Regulates Insulin Receptor Substrates 1 and 2 through Up-Regulation of Suppressor of Cytokine Signaling 3

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