scholarly journals Hepatitis C Virus (HCV) Quasispecies Complexity and Selection in HCV/HIV‐Coinfected Subjects Treated with Interferon‐Based Regimens

2010 ◽  
pp. 100127142343070-000
Author(s):  
Kenneth E. Sherman ◽  
Susan D. Rouster ◽  
Sandra Stanford ◽  
Jason T. Blackard ◽  
Norah Shire ◽  
...  
Keyword(s):  
Hepatitis C Virus ◽  
Hepatitis C ◽  
Quasispecies Complexity

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

2000 ◽  
Vol 74 (2) ◽  
pp. 805-811 ◽  
Author(s):  
Beatriz Cabot ◽  
María Martell ◽  
Juan I. Esteban ◽  
Sílvia Sauleda ◽  
Teresa Otero ◽  
...  
Keyword(s):  
Hepatitis C Virus ◽  
Hepatitis C ◽  
Amino Acid ◽  
Amino Acid Sequences ◽  
Reverse Transcription Pcr ◽  
Extrahepatic Replication ◽  
Viral Heterogeneity ◽  
Selective Forces ◽  
Paired Serum ◽  
Quasispecies Complexity

ABSTRACT 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.

scholarly journals Acute Hepatitis C Virus Structural Gene Sequences as Predictors of Persistent Viremia: Hypervariable Region 1 as a Decoy

1999 ◽  
Vol 73 (4) ◽  
pp. 2938-2946 ◽  
Author(s):  
Stuart C. Ray ◽  
Yu-Ming Wang ◽  
Oliver Laeyendecker ◽  
John R. Ticehurst ◽  
Stephen A. Villano ◽  
...  
Keyword(s):  
Hepatitis C Virus ◽  
Hepatitis C ◽  
Selective Pressure ◽  
Hypervariable Region ◽  
Amino Acid Sequences ◽  
Heteroduplex Analysis ◽  
Acute Hepatitis C ◽  
Hypervariable Region 1 ◽  
Persistent Viremia ◽  
Quasispecies Complexity

ABSTRACT We hypothesized that hepatitis C virus (HCV) persistence is related to the sequence variability of putative envelope genes. This hypothesis was tested by characterizing quasispecies in specimens collected every six months from a cohort of acutely HCV-infected subjects (mean duration of specimen collection, 72 months after seroconversion). We evaluated 5 individuals who spontaneously cleared viremia and 10 individuals with persistent viremia by cloning 33 1-kb amplicons that spanned E1 and the 5′ half of E2, including hypervariable region 1 (HVR1). To assess the quasispecies complexity and to detect variants for sequencing, the first PCR-positive sample was examined by using a previously described method that combines heteroduplex analysis and analysis of single-stranded conformational polymorphisms. The ratio of nonsynonymous to synonymous substitutions (dN/dS ) within each sample was evaluated as an indicator of relative selective pressure. Amino acid sequences were analyzed for signature patterns, glycosylation signals, and charge. Quasispecies complexity was higher and E1dN/dS ratios (selective pressure) were lower in those with persistent viremia; the association with persistence was strengthened by the presence of a combination of both characteristics. In contrast, a trend toward higher HVR1dN/dS ratios was detected among those with persistent viremia. We did not detect any such association for factors that may affect complexity such as serum HCV RNA concentration. HVR1 had a lower positive charge in subjects with persistent viremia, although no consistent motifs were detected. Our data suggest that HCV persistence is associated with a complex quasispecies and immune response to HVR1.

scholarly journals Hypervariable Region 1 Sequence Stability during Hepatitis C Virus Replication in Chimpanzees

2000 ◽  
Vol 74 (7) ◽  
pp. 3058-3066 ◽  
Author(s):  
Stuart C. Ray ◽  
Qing Mao ◽  
Robert E. Lanford ◽  
Suzanne Bassett ◽  
Oliver Laeyendecker ◽  
...  
Keyword(s):  
Hepatitis C Virus ◽  
Hepatitis C ◽  
Selection Pressure ◽  
Hypervariable Region ◽  
Variable Region ◽  
Nonsynonymous Substitution ◽  
Hypervariable Region 1 ◽  
Single Stranded Conformational Polymorphism ◽  
Quasispecies Complexity ◽  
Selection Of

ABSTRACT The putative envelope 2 (E2) gene of hepatitis C virus (HCV) contains a highly variable region referred to as hypervariable region 1 (HVR1). We hypothesized that this genetic variability is driven by immune selection pressure, rather than representing the accumulation of random mutations in a region with relatively little functional constraint. To test this hypothesis, we examined the E2 sequence of a human inoculum that was passaged through eight chimpanzees, which appear to have a replicative rate (opportunity for chance mutation) similar to that of humans. Acute-phase plasma samples from a human (the inoculum) and six of eight serially infected chimpanzees were studied. For each, 33 cloned cDNAs were examined by a combined heteroduplex–single-stranded conformational polymorphism assay to assess quasispecies complexity and optimize selection of clones with unique gel shift patterns (clonotypes) for sequencing. The sequence diversity of HCV was significantly lower in the chimpanzees than in the humans, and during eight serial passages there was no change in the sequence of the majority clonotype from each animal examined. Similarly, the rates of protein sequence altering (nonsynonymous) substitution were lower in the chimpanzees than in the humans. These findings demonstrate that nonsynonymous mutations indicate selection pressure rather than being an incidental result of HCV replication.

scholarly journals Evolutionary trends of the first hypervariable region of the hepatitis C virus E2 protein in individuals with differing liver disease severity

2002 ◽  
Vol 83 (1) ◽  
pp. 11-23 ◽  
Author(s):  
Rebecca Curran ◽  
Claire L. Jameson ◽  
Joanna K. Craggs ◽  
Anna M. Grabowska ◽  
Brian J. Thomson ◽  
...  
Keyword(s):  
Hepatitis C Virus ◽  
Liver Disease ◽  
Hepatitis C ◽  
Disease Severity ◽  
Acute Infection ◽  
Hypervariable Region ◽  
Virus Population ◽  
Rates Of Evolution ◽  
Progressive Liver Disease ◽  
Quasispecies Complexity

Hepatitis C virus (HCV) exists as a complex swarm of genetically related viruses known as a quasispecies. Recent work has shown that quasispecies complexity and evolutionary rates are associated with the outcome of acute infection. Knowledge of how the virus population evolves at different stages of chronic infection is less clear. We have studied rates of evolution of the first hypervariable region (HVR1) of the E2 envelope protein in six individuals with disparate liver disease severity. These data show that virus populations present in individuals with mild non-progressive liver disease evolve in a typical Darwinian fashion, with a consistent accumulation of non-synonymous (amino acid-changing) substitutions. By contrast, the virus population remains relatively static in individuals with severe progressive liver disease. Possible mechanisms for this disparity are discussed.

Dynamics of serum hepatitis C virus load and quasispecies complexity during antiviral therapy in patients with chronic hepatitis C

2001 ◽  
Vol 20 (1-2) ◽  
pp. 85-89 ◽  
Author(s):  
Blazenka Grahovac ◽  
Jasna Bingulac-Popovic ◽  
Boris Vucelic ◽  
Irena Hrstic ◽  
Rajko Ostojic ◽  
...  
Keyword(s):  
Chronic Hepatitis ◽  
Hepatitis C Virus ◽  
Hepatitis C ◽  
Antiviral Therapy ◽  
Chronic Hepatitis C ◽  
Serum Hepatitis ◽  
Virus Load ◽  
Quasispecies Complexity

HEPATITIS C VIRUS INFECTION (AND ADDITIONAL NEOPLASMS) AMONG MARGINAL ZONE LYMPHOMAS

1997 ◽  
Vol 96 (2) ◽  
pp. 427-428 ◽  
Author(s):  
FREDERICO SILVESTRI ◽  
GIOVANNI BARILLARI ◽  
RENATO FANIN ◽  
FLAVIA SALMASO ◽  
LAURA INFANTI ◽  
...  
Keyword(s):  
Hepatitis C Virus ◽  
Hepatitis C ◽  
Virus Infection ◽  
Marginal Zone ◽  
Hepatitis C Virus Infection
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