The Experts below are selected from a list of 327 Experts worldwide ranked by ideXlab platform

Howard C Thomas - One of the best experts on this subject based on the ideXlab platform.

  • Hypervariable Region of hepatitis c virus envelope glycoprotein e2 ns1 in an agammaglobulinemic patient
    Gastroenterology, 1994
    Co-Authors: Umesh Kumar, John Monjardino, Howard C Thomas
    Abstract:

    In an agammaglobulinemic patient with chronic hepatitis C, a previously identified Hypervariable Region of the major envelope glycoprotein remained unchanged for 2.5 years. Serum-derived RNA amplified by reverse transcription-polymerase chain reaction was cloned in a bacterial vector, and a minimum of three independent clones were sequenced by dideoxy chain termination reaction. Comparison of consensus sequences from three different time points during the chronic phase of infection showed absolute homology at both amino acid and nucleotide levels. This finding provides support for the role of antibody selection in generating genetic variation and viral persistence; also, it is consistent with the hypothesis that an epitope within this Region is the site of virus neutralization. The observations show that the hepatitis seen in hepatitis C virus infection is not dependent on the humoral immune response.

  • Hypervariable Region of Hepatitis C Virus Envelope Glycoprotein (E2/NSl) in an Agammaglobulinemic Patient
    1994
    Co-Authors: Umesh Kumar, John Monjardino, Howard C Thomas
    Abstract:

    In an agammaglobulinemic patient with chronic hepatitis C, a previously identified Hypervariable Region of the major envelope glycoprotein remained unchanged for 2.5 years. Serum-derived RNA amplified by reverse transcription-polymerase chain reaction was cloned in a bacterial vector, and a minimum of three independent clones were sequenced by dideoxy chain termination reaction. Comparison of consensus sequences from three different time points during the chronic phase of infection showed absolute homology at both amino acid and nucleotide levels. This finding provides support for the role of antibody selection in generating genetic variation and viral persistence; also, it is consistent with the hypothesis that an epitope within this Region is the site of virus neutralization. The observations show that the hepatitis seen in hepatitis C virus infection is not dependent on the humoral immune response.

  • Hypervariable Region of hepatitis C virus envelope glycoprotein (E2/NS1) in an agammaglobulinemic patient.
    Gastroenterology, 1994
    Co-Authors: Umesh Kumar, John Monjardino, Howard C Thomas
    Abstract:

    In an agammaglobulinemic patient with chronic hepatitis C, a previously identified Hypervariable Region of the major envelope glycoprotein remained unchanged for 2.5 years. Serum-derived RNA amplified by reverse transcription-polymerase chain reaction was cloned in a bacterial vector, and a minimum of three independent clones were sequenced by dideoxy chain termination reaction. Comparison of consensus sequences from three different time points during the chronic phase of infection showed absolute homology at both amino acid and nucleotide levels. This finding provides support for the role of antibody selection in generating genetic variation and viral persistence; also, it is consistent with the hypothesis that an epitope within this Region is the site of virus neutralization. The observations show that the hepatitis seen in hepatitis C virus infection is not dependent on the humoral immune response.

Fumiaki Marumo - One of the best experts on this subject based on the ideXlab platform.

  • Comparison of the Hypervariable Region of hepatitis C virus genomes in plasma and liver
    Journal of medical virology, 1995
    Co-Authors: Naoya Sakamoto, Nobuyuki Enomoto, Masayuki Kurosaki, Yasuhiro Asahina, Shinya Maekawa, Kazuhiko Koizumi, Ikuo Sakuma, Takeshi Murakami, Fumiaki Marumo, Chifumi Sato
    Abstract:

    Nucleotide sequences of the Hypervariable Region of hepatitis C virus genomes obtained from plasma change rapidly during the course of infection and are believed to play a part in immunological escape and consequently in the development of persistent infection. It is not known, however, whether these changes also occur in the liver. To clarify this aspect, RNA was extracted from the plasma and liver tissue of eight patients with chronic hepatitis C. After cDNA synthesis, DNA fragments that included the Hypervariable Region were amplified by the polymerase chain reaction. Consensus nucleotide sequences were determined directly from the polymerase chain reaction products by the dideoxy chain termination method. The diversity of the Hypervariable Region was analyzed further by the polymerase chain reaction-single strand conformation polymorphism analysis. Consensus nucleotide sequences of the Hypervariable Region were identical between the plasma and the liver in each patient. The polymerase chain reaction-single strand conformation polymorphism analysis showed multiple DNA bands that represented different Hypervariable Region sequences. Comparison of the single strand conformation polymorphism patterns revealed that the number, the mobility, and the density of bands were the same between the plasma and the liver. It is concluded that the population and the diversity of hepatitis C virus quasispecies as detected by the Hypervariable Region sequence are the same between the plasma and the liver despite rapid mutations, indicating that rapid changes in the population of hepatitis C virus quasispecies also occur in the liver.

  • Hepatitis C virus after interferon treatment has the variation in the Hypervariable Region of envelope 2 gene
    Journal of hepatology, 1994
    Co-Authors: Nobuyuki Enomoto, Masayuki Kurosaki, Chifumi Sato, Fumiaki Marumo
    Abstract:

    There is a Hypervariable Region in the envelope 2 gene of the hepatitis C virus genome, whose heterogeneity in different hepatitis C virus isolates has been suggested to be a result of the immune selection of escape variants. To determine the role of Hypervariable Region variants in the mechanism of resistance to interferon observed in 75-80% of interferon-treated patients with chronic hepatitis C, Hypervariable Region sequences were compared before and after interferon treatment. Eight patients with chronic hepatitis C were treated with recombinant interferon-alpha-2b. DNA containing the Hypervariable Region was obtained by reverse transcription-polymerase chain reaction from serial plasma samples of each patient and directly sequenced without cloning to determine changes in the predominant sequence. In two patients, hepatitis C virus-RNA was eliminated by interferon treatment. In the remaining six patients, hepatitis C virus-RNA was not eradicated. The predominant hepatitis C virus which survived interferon treatment was the mutant hepatitis C virus with 3-19 out of 81 nucleotide substitutions in the Hypervariable Region, resulting in 2-14 out of 27 amino acid changes. Most of the nucleotide substitutions were nonsynonymous, indicating that there were positive selections for amino acid changes in the Hypervariable Region. The change rate was significantly higher in patients whose plasma hepatitis C virus-RNA was consistently detectable during and after interferon treatment than in patients whose plasma hepatitis C virus-RNA became undetectable during treatment and reappeared after the cessation of the treatment (4.23 +/- 0.43 vs 0.77 +/- 0.20 x 10(-1)/site/year, p < 0.01). This suggests that the evolution of the Hypervariable Region was associated with the effect of interferon treatment. These results suggest that Hypervariable Region variants play an important role in maintaining persistent infection during interferon treatment by evading host immune surveillance.

  • Rapid sequence variation of the Hypervariable Region of hepatitis C virus during the course of chronic infection
    Hepatology (Baltimore Md.), 1993
    Co-Authors: Masayuki Kurosaki, Nobuyuki Enomoto, Fumiaki Marumo, Chifumi Sato
    Abstract:

    To evaluate the clinical significance of sequence variations in the Hypervariable Region of hepatitis C virus during the course of chronic infection, we performed pairwise comparison of the predominant nucleotide sequences. Hepatitis C virus RNA was extracted from two plasma samples obtained from 12 chronically infected Japanese patients over approximately 1 yr. Complementary DNA containing the Hypervariable Region was amplified by means of reverse transcription-polymerase chain reaction and was directly sequenced for determination of predominant sequences. In all 12 individuals, the predominant sequence of the Hypervariable Region at the second time point differed from that at the first time point, and significant sequence variation was observed during this short period. A high proportion of these nucleotide substitutions (90%) resulted in changes of predicted amino acid sequences, indirect evidence of in vivo positive selection for these variants. There appeared to be an important difference in the rate of nucleotide sequence variation of the Hypervariable Region between four patients with flare-ups of their ALT levels (1.54 to 2.24 x 10(-1)/genome site/yr) and eight patients with quiescent courses (0.13 to 1.21 x 10(-1)/genome site/yr). These results demonstrate that rapid sequence variations of the Hypervariable Region of predominant virus population take place during the natural course of chronic hepatitis C virus infection. These sequence variations seem to occur as an adaptive response of hepatitis C virus to evade host immunity and may play a major role in the establishment of persistent infection and in the occasional flare-up of hepatitis.

Umesh Kumar - One of the best experts on this subject based on the ideXlab platform.

  • Hypervariable Region of hepatitis c virus envelope glycoprotein e2 ns1 in an agammaglobulinemic patient
    Gastroenterology, 1994
    Co-Authors: Umesh Kumar, John Monjardino, Howard C Thomas
    Abstract:

    In an agammaglobulinemic patient with chronic hepatitis C, a previously identified Hypervariable Region of the major envelope glycoprotein remained unchanged for 2.5 years. Serum-derived RNA amplified by reverse transcription-polymerase chain reaction was cloned in a bacterial vector, and a minimum of three independent clones were sequenced by dideoxy chain termination reaction. Comparison of consensus sequences from three different time points during the chronic phase of infection showed absolute homology at both amino acid and nucleotide levels. This finding provides support for the role of antibody selection in generating genetic variation and viral persistence; also, it is consistent with the hypothesis that an epitope within this Region is the site of virus neutralization. The observations show that the hepatitis seen in hepatitis C virus infection is not dependent on the humoral immune response.

  • Hypervariable Region of Hepatitis C Virus Envelope Glycoprotein (E2/NSl) in an Agammaglobulinemic Patient
    1994
    Co-Authors: Umesh Kumar, John Monjardino, Howard C Thomas
    Abstract:

    In an agammaglobulinemic patient with chronic hepatitis C, a previously identified Hypervariable Region of the major envelope glycoprotein remained unchanged for 2.5 years. Serum-derived RNA amplified by reverse transcription-polymerase chain reaction was cloned in a bacterial vector, and a minimum of three independent clones were sequenced by dideoxy chain termination reaction. Comparison of consensus sequences from three different time points during the chronic phase of infection showed absolute homology at both amino acid and nucleotide levels. This finding provides support for the role of antibody selection in generating genetic variation and viral persistence; also, it is consistent with the hypothesis that an epitope within this Region is the site of virus neutralization. The observations show that the hepatitis seen in hepatitis C virus infection is not dependent on the humoral immune response.

  • Hypervariable Region of hepatitis C virus envelope glycoprotein (E2/NS1) in an agammaglobulinemic patient.
    Gastroenterology, 1994
    Co-Authors: Umesh Kumar, John Monjardino, Howard C Thomas
    Abstract:

    In an agammaglobulinemic patient with chronic hepatitis C, a previously identified Hypervariable Region of the major envelope glycoprotein remained unchanged for 2.5 years. Serum-derived RNA amplified by reverse transcription-polymerase chain reaction was cloned in a bacterial vector, and a minimum of three independent clones were sequenced by dideoxy chain termination reaction. Comparison of consensus sequences from three different time points during the chronic phase of infection showed absolute homology at both amino acid and nucleotide levels. This finding provides support for the role of antibody selection in generating genetic variation and viral persistence; also, it is consistent with the hypothesis that an epitope within this Region is the site of virus neutralization. The observations show that the hepatitis seen in hepatitis C virus infection is not dependent on the humoral immune response.

Adrian M. Di Bisceglie - One of the best experts on this subject based on the ideXlab platform.

  • Diversification of Hypervariable Region 1 of hepatitis C virus after liver transplantation.
    Journal of medical virology, 2003
    Co-Authors: Xiaofeng Fan, Adrian M. Di Bisceglie
    Abstract:

    Liver transplantation represents a unique model for studying hepatitis C virus (HCV) evolution. In the current study, we estimated the dynamics of HCV quasispecies evolution over a period of 2.5 years both in sera and in tissues, including three different anatomic sites of the liver in a patient undergoing liver transplantation. The patient displayed an extremely homologous virus population in either serum or liver at each time point after liver transplantation. However, there was a successive diversification of Hypervariable Region 1 (HVR1) of HCV under such an im-munocompromised status and the preexistence of matching HVR1 antibodies. This distinct evolutionary pattern of HVR1 suggests that immunosuppressed status does contribute to diminished genetic diversity of HVR1 at a given time point after liver transplantation. However, the dramatic diversification of HVR1 sequence over time is mainly due to the adaptation of new replicative site, the donor liver, indicating that HCV may obtain the higher replication fitness by mutating HVR1 domain. J. Med. Virol. 70: 212–218, 2003. © 2003 Wiley-Liss, Inc.

  • Differential amplification of Hypervariable Region 1 of hepatitis C virus by partially mismatched primers.
    Biochemical and biophysical research communications, 2001
    Co-Authors: Xiaofeng Fan, Andre C. Lyra, De Tan, Adrian M. Di Bisceglie
    Abstract:

    The quasispecies nature of hepatitis C virus (HCV) has been well documented over its whole genome and the most variable domain is located at the 5' end of the second envelope Region, the so-called Hypervariable Region 1 (HVR1). HVR1 has therefore been extensively used as the target for characterizing HCV quasispecies profiles. In this study, we reported our finding that partially mismatched primers preferentially amplify different HVR1 sequences in a heterogeneous virus population. This finding suggests a possible mechanism of bias during the amplification of HVR1 sequences and may be responsible for some conflicting data regarding evolutionary or clinical implications of HCV quasispecies.

  • Genetic characterization of Hypervariable Region 1 in patients chronically infected with hepatitis C virus genotype 2.
    Journal of medical virology, 2001
    Co-Authors: Xiaofeng Fan, Adrian M. Di Bisceglie
    Abstract:

    The Hypervariable Region 1 (HVR1) has been most reliably identified in the genome of HCV genotype 1 isolates and thought to possibly play a role in immune evasion and development of chronic infection. There are few studies, however, of other HCV genotypes to determine if they also have such a Hypervariable Region present, and it is unclear whether or not there is any genotype-dependent difference in the genetic characteristics of HVR1. We determined the nucleotide sequence of 5' end of E2/NS1 Region of the HCV genome spanning HVR1 of multiple genotype 1 and 2 HCV isolates and carried out a detailed genetic analysis. Similarity plots identified two Hypervariable Regions within the genotype 2 sequences, a larger one corresponding to HVR1 as well as a smaller 27-nucleotide Region of hypervariability. The synonymous substitutions per synonymous site (ds) was greater than nonsynonymous substitutions per nonsynonymous site (dn) within genotype 1 group whereas dn and ds were similar in the genotype 2 group. Analysis of amino acid sequences revealed several conserved sites across genotype 1 and 2 (amino acid numbers 2,6, 20 and 26) and overall similar hydropathic profiles were found within two genotypes. Still, despite the hypervariability, the HVR1 showed a genotype-specific phylogenetic clustering. Thus, HVR1 appears to be conserved between genotypes in keeping with it having an important survival function. Genotype 2 appears to have a greater rate of nonsynonymous substitutions within HVR1, suggesting a greater positive evolutionary pressure.

Chifumi Sato - One of the best experts on this subject based on the ideXlab platform.

  • Comparison of the Hypervariable Region of hepatitis C virus genomes in plasma and liver
    Journal of medical virology, 1995
    Co-Authors: Naoya Sakamoto, Nobuyuki Enomoto, Masayuki Kurosaki, Yasuhiro Asahina, Shinya Maekawa, Kazuhiko Koizumi, Ikuo Sakuma, Takeshi Murakami, Fumiaki Marumo, Chifumi Sato
    Abstract:

    Nucleotide sequences of the Hypervariable Region of hepatitis C virus genomes obtained from plasma change rapidly during the course of infection and are believed to play a part in immunological escape and consequently in the development of persistent infection. It is not known, however, whether these changes also occur in the liver. To clarify this aspect, RNA was extracted from the plasma and liver tissue of eight patients with chronic hepatitis C. After cDNA synthesis, DNA fragments that included the Hypervariable Region were amplified by the polymerase chain reaction. Consensus nucleotide sequences were determined directly from the polymerase chain reaction products by the dideoxy chain termination method. The diversity of the Hypervariable Region was analyzed further by the polymerase chain reaction-single strand conformation polymorphism analysis. Consensus nucleotide sequences of the Hypervariable Region were identical between the plasma and the liver in each patient. The polymerase chain reaction-single strand conformation polymorphism analysis showed multiple DNA bands that represented different Hypervariable Region sequences. Comparison of the single strand conformation polymorphism patterns revealed that the number, the mobility, and the density of bands were the same between the plasma and the liver. It is concluded that the population and the diversity of hepatitis C virus quasispecies as detected by the Hypervariable Region sequence are the same between the plasma and the liver despite rapid mutations, indicating that rapid changes in the population of hepatitis C virus quasispecies also occur in the liver.

  • Hepatitis C virus after interferon treatment has the variation in the Hypervariable Region of envelope 2 gene
    Journal of hepatology, 1994
    Co-Authors: Nobuyuki Enomoto, Masayuki Kurosaki, Chifumi Sato, Fumiaki Marumo
    Abstract:

    There is a Hypervariable Region in the envelope 2 gene of the hepatitis C virus genome, whose heterogeneity in different hepatitis C virus isolates has been suggested to be a result of the immune selection of escape variants. To determine the role of Hypervariable Region variants in the mechanism of resistance to interferon observed in 75-80% of interferon-treated patients with chronic hepatitis C, Hypervariable Region sequences were compared before and after interferon treatment. Eight patients with chronic hepatitis C were treated with recombinant interferon-alpha-2b. DNA containing the Hypervariable Region was obtained by reverse transcription-polymerase chain reaction from serial plasma samples of each patient and directly sequenced without cloning to determine changes in the predominant sequence. In two patients, hepatitis C virus-RNA was eliminated by interferon treatment. In the remaining six patients, hepatitis C virus-RNA was not eradicated. The predominant hepatitis C virus which survived interferon treatment was the mutant hepatitis C virus with 3-19 out of 81 nucleotide substitutions in the Hypervariable Region, resulting in 2-14 out of 27 amino acid changes. Most of the nucleotide substitutions were nonsynonymous, indicating that there were positive selections for amino acid changes in the Hypervariable Region. The change rate was significantly higher in patients whose plasma hepatitis C virus-RNA was consistently detectable during and after interferon treatment than in patients whose plasma hepatitis C virus-RNA became undetectable during treatment and reappeared after the cessation of the treatment (4.23 +/- 0.43 vs 0.77 +/- 0.20 x 10(-1)/site/year, p < 0.01). This suggests that the evolution of the Hypervariable Region was associated with the effect of interferon treatment. These results suggest that Hypervariable Region variants play an important role in maintaining persistent infection during interferon treatment by evading host immune surveillance.

  • Rapid sequence variation of the Hypervariable Region of hepatitis C virus during the course of chronic infection
    Hepatology (Baltimore Md.), 1993
    Co-Authors: Masayuki Kurosaki, Nobuyuki Enomoto, Fumiaki Marumo, Chifumi Sato
    Abstract:

    To evaluate the clinical significance of sequence variations in the Hypervariable Region of hepatitis C virus during the course of chronic infection, we performed pairwise comparison of the predominant nucleotide sequences. Hepatitis C virus RNA was extracted from two plasma samples obtained from 12 chronically infected Japanese patients over approximately 1 yr. Complementary DNA containing the Hypervariable Region was amplified by means of reverse transcription-polymerase chain reaction and was directly sequenced for determination of predominant sequences. In all 12 individuals, the predominant sequence of the Hypervariable Region at the second time point differed from that at the first time point, and significant sequence variation was observed during this short period. A high proportion of these nucleotide substitutions (90%) resulted in changes of predicted amino acid sequences, indirect evidence of in vivo positive selection for these variants. There appeared to be an important difference in the rate of nucleotide sequence variation of the Hypervariable Region between four patients with flare-ups of their ALT levels (1.54 to 2.24 x 10(-1)/genome site/yr) and eight patients with quiescent courses (0.13 to 1.21 x 10(-1)/genome site/yr). These results demonstrate that rapid sequence variations of the Hypervariable Region of predominant virus population take place during the natural course of chronic hepatitis C virus infection. These sequence variations seem to occur as an adaptive response of hepatitis C virus to evade host immunity and may play a major role in the establishment of persistent infection and in the occasional flare-up of hepatitis.