The Impact of Rapid Evolution of the Hepatitis Viruses

Esteban, Juan Ignacio; Martell, Marı́a; Carman, William F.; Gómez, Jordi

doi:10.1016/b978-012220360-2/50014-3

Cited by 12 publications

(14 citation statements)

References 221 publications

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“…The uncertainty of the genetic identity of the viral agent is maintained, both in space (serum and liver) and in time, throughout the infection. Our understanding of the viral life cycle relies on the knowledge of the behavior and relationships among components of the population of individuals, which, in turn, might help in understanding viral persistence and failure of treatment (1,3,13,14,39). In an attempt to define the continuity of the genetic constitution of the viral quasispecies in space and time, we analyzed series of sequential liver and serum samples in four patients with chronic hepatitis C.…”

Section: Discussionmentioning

confidence: 99%

“…It is well known that the evolutionary potential of the HCV genome varies markedly at different loci depending on structural and functional constraints (i.e., those of the 5Ј-noncoding region) and positive selective forces such as that of the immune system on the hypervariable region of E2 (14,36,37). It is possible that the quasispecies fluctuation of the genomic region here investigated is a consequence of selective forces acting at other functional or antigenic regions of the encoded HCV proteins, favoring replication of a specific sequence subset from those present in the liver.…”

Section: Discussionmentioning

confidence: 99%

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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: 99%

Section: Discussionmentioning

confidence: 99%

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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“…It has been experimentally proven for RNA phage (14) and viruses (27) that the use of this formula is intended to produce successful adaptation to environmental changes (12). This mechanism has been invoked in the HCV virus model to explain both the high frequency of viral persistence and the wide range of disease (3,4,10,18,21,39). Phylogenetic methods may be used for understanding virus evolution.…”

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confidence: 99%

Nucleotide and Amino Acid Complexity of Hepatitis C Virus Quasispecies in Serum and Liver

Cabot

Martell

Esteban

et al. 2000

J Virol

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The quasispecies nature of the hepatitis C virus (HCV) is thought to play a central role in maintaining and modulating viral replication. Several studies have tried to unravel, through the parameters that characterize HCV circulating quasispecies, prognostic markers of the disease. In a previous work we demonstrated that the parameters of circulating viral quasispecies do not always reflect those of the intrahepatic virus. Here, we have analyzed paired serum and liver quasispecies from 39 genotype 1b-infected patients with different degrees of liver damage, ranging from minimal changes to cirrhosis. Viral level was quantified by real-time reverse transcription-PCR, and viral heterogeneity was characterized through the cloning and sequencing of 540 HCV variants of a genomic fragment encompassing the E2-NS2 junction. Although in 95% of patients, serum and liver consensus HCV amino acid sequences were identical, quasispecies complexity varied considerably between the viruses isolated from each compartment. Patients with HCV quasispecies in serum more complex (26%) than, less complex (28%) than, or similarly complex (41%) to those in liver were found. Among the last, a significant correlation between fibrosis and all the parameters that measure the viral amino acid complexity was found. Correlation between fibrosis and serum viral load was found as well (R ‫؍‬ 0.7). With regard to the origin of the differences in quasispecies complexity between serum and liver populations, sequence analysis argued against extrahepatic replication as a quantitatively important contributing factor and supported the idea of a differential effect or different selective forces on the virus depending on whether it is circulating in serum or replicating in the liver. Flaviviridae (7,29,45). Its genome consists of a single-stranded RNA, with plus polarity, of 9,600 nucleotides, which does not integrate in the host genome, yet persistence is the rule. The damage caused during infection ranges from minimal changes to cirrhosis of the liver and hepatocarcinoma, but little is known about the mechanism of hepatocyte injury due to chronic infection. It seems very likely that the pathogenesis of HCV infection is directly related to a strong interplay between the host defense mechanisms and the virus's ability to evade them efficiently. Moreover, in order to persist, HCV must regulate its lytic potential and avoid elimination by the host immune system. Due to the quasispecies structure of the HCV viral population infecting single patients (39), the virus may use a variety of strategies to fulfill both requirements (11,17). Hepatitis C virus (HCV) is an enveloped virus classified in the familyThe dynamic component of the quasispecies structure is responsible for the rapid virus evolution (12). It works through a complex mixture of genomic sequences (quasispecies) which behaves as a single unit when facing changes in the environment. The genetic interaction within the viral population allows the system to distinguish the best possibility at any given...

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“…Between strains, ayw and adw subtypes demonstrate considerable genetic heterogeneity [2]. Genotypes and subtypes probably evolved in ethnic backgrounds over centuries [6] and the relationship of these ten subtypes to genomic groups A -H has been established.…”

Section: Introductionmentioning

confidence: 99%

Hepatitis B virus genotypes, core gene variability and ethnicity in the Pacific region

Jazayeri

Basuni

Cooksley

et al. 2004

Journal of Hepatology

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The Impact of Rapid Evolution of the Hepatitis Viruses

Cited by 12 publications

References 221 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

Nucleotide and Amino Acid Complexity of Hepatitis C Virus Quasispecies in Serum and Liver

Hepatitis B virus genotypes, core gene variability and ethnicity in the Pacific region

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