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Virology

Variability of the Polymerase Gene (NS5B) in Hepatitis C Virus-Infected Women

Jason T. Blackard, Gang Ma, Berkeley N. Limketkai, Jeffrey A. Welge, Peter D. Dryer, Christina M. Martin, Yoichi Hiasa, Lynn E. Taylor, Kenneth H. Mayer, Denise J. Jamieson, Kenneth E. Sherman
Jason T. Blackard
1Department of Internal Medicine, Division of Digestive Diseases, University of Cincinnati College of Medicine, Cincinnati, Ohio
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  • For correspondence: jason.blackard@uc.edu
Gang Ma
1Department of Internal Medicine, Division of Digestive Diseases, University of Cincinnati College of Medicine, Cincinnati, Ohio
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Berkeley N. Limketkai
1Department of Internal Medicine, Division of Digestive Diseases, University of Cincinnati College of Medicine, Cincinnati, Ohio
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Jeffrey A. Welge
2Departments of Psychiatry and Environmental Health, University of Cincinnati College of Medicine, Cincinnati, Ohio
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Peter D. Dryer
1Department of Internal Medicine, Division of Digestive Diseases, University of Cincinnati College of Medicine, Cincinnati, Ohio
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Christina M. Martin
1Department of Internal Medicine, Division of Digestive Diseases, University of Cincinnati College of Medicine, Cincinnati, Ohio
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Yoichi Hiasa
3Department of Gastroenterology and Metabology, Ehime University Graduate School of Medicine, Ehime, Japan
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Lynn E. Taylor
4Miriam Hospital and Department of Medicine, Brown University, Providence, Rhode Island
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Kenneth H. Mayer
4Miriam Hospital and Department of Medicine, Brown University, Providence, Rhode Island
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Denise J. Jamieson
5Division of Reproductive Health, Centers for Disease Control and Prevention, Atlanta, Georgia
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Kenneth E. Sherman
1Department of Internal Medicine, Division of Digestive Diseases, University of Cincinnati College of Medicine, Cincinnati, Ohio
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DOI: 10.1128/JCM.01613-10
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    FIG. 1.

    Sequence logo diagram (http://weblogo.berkeley.edu ) showing amino acids 227 through 340 of the HCV NS5B protein from 26 genotype 1a consensus sequences. Numbers shown below the sequence represent the amino acid position in the complete HCV polyprotein. For polymorphic sites (i.e., those with more than one letter shown per position), the height of each letter represents the relative proportion of each amino acid at that position.

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  • TABLE 1.

    Codons under positive or negative selection pressure among 29 HCV-seropositive women with genotype 1 based on the FEL and REL methods

    Patient no.Codon no. based on FEL witha: Codon no. based on REL witha:
    Positive selectionNegative selectionPositive selectionNegative selection
    62NoneNoneNone2785, 2788
    90NoneNoneNoneNone
    106NoneNoneNoneNone
    116None2771NoneNone
    119NoneNoneNoneNone
    124NoneNoneNoneNone
    135None 2733 , 2769 None2718, 2722, 2733, 2737, 2764, 2769 , 2790, 2792, 2813, 2817
    149NoneNoneNoneNone
    184NoneNoneNoneNone
    186NoneNoneNoneNone
    199NoneNoneNoneNone
    211None2761None2719, 2743, 2750, 2754, 2761, 2769 , 2776, 2781, 2786, 2795, 2798, 2810, 2815
    217NoneNoneNoneNone
    220NoneNone2818None
    230None2715NoneNone
    249NoneNoneNoneNone
    269NoneNone2807None
    282NoneNoneNoneNone
    285None 2747 None2742, 2747 , 2780 , 2784
    287NoneNoneNoneNone
    304None2717, 2738NoneNone
    340None2809NoneNone
    383NoneNoneNone2708, 2817 , 2818
    389NoneNoneNoneNone
    392NoneNoneNone2712, 2715, 2766, 2797, 2800 , 2804, 2805, 2811, 2816
    394None 2733 NoneNone
    504None2728, 2747 , 2761, 2769 None2728, 2747 , 2756, 2769 , 2775, 2780 , 2800
    514NoneNoneNoneNone
    520NoneNoneNoneNone
    • ↵ a Codons under positive or negative selection pressure among 29 HCV-seropositive women with genotype 1. Shown are codons with a significance of P ≤0.05 (FEL method) or posterior probability of ≥0.99 (REL method). Codons detected in more than one individual are underlined.

  • TABLE 2.

    Correlation of NS5B intrapatient diversity with clinical variables among 29 HCV-infected women

    ComparisonSpearman correlation coefficientP valuea
    NS5B genetic distance vs HCV RNA0.286NS
    NS5B entropy vs HCV RNA0.163NS
    NS5B dN − dS vs HCV RNA−0.4920.007
    NS5B genetic distance vs CD4 cell count−0.033NS
    NS5B entropy vs CD4 cell count0.186NS
    NS5B dN − dS vs CD4 cell count0.3870.056
    NS5B genetic distance vs ALT−0.222NS
    NS5B entropy vs ALT−0.002NS
    NS5B dN − dS vs ALT0.199NS
    NS5B genetic distance vs AST−0.178NS
    NS5B entropy vs AST−0.144NS
    NS5B dN − dS vs AST0.165NS
    NS5B genetic distance vs HIV viral load0.122NS
    NS5B entropy vs HIV viral load−0.079NS
    NS5B dN − dS vs HIV viral load−0.142NS
    • ↵ a P values of <0.10 are shown. NS, not significant.

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Variability of the Polymerase Gene (NS5B) in Hepatitis C Virus-Infected Women
Jason T. Blackard, Gang Ma, Berkeley N. Limketkai, Jeffrey A. Welge, Peter D. Dryer, Christina M. Martin, Yoichi Hiasa, Lynn E. Taylor, Kenneth H. Mayer, Denise J. Jamieson, Kenneth E. Sherman
Journal of Clinical Microbiology Oct 2010, 48 (11) 4256-4259; DOI: 10.1128/JCM.01613-10

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Variability of the Polymerase Gene (NS5B) in Hepatitis C Virus-Infected Women
Jason T. Blackard, Gang Ma, Berkeley N. Limketkai, Jeffrey A. Welge, Peter D. Dryer, Christina M. Martin, Yoichi Hiasa, Lynn E. Taylor, Kenneth H. Mayer, Denise J. Jamieson, Kenneth E. Sherman
Journal of Clinical Microbiology Oct 2010, 48 (11) 4256-4259; DOI: 10.1128/JCM.01613-10
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KEYWORDS

Genetic Variation
Hepacivirus
hepatitis C
Viral Nonstructural Proteins

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