Genetic and functional heterogeneity of the hepatitis C virus p7 ion channel during natural chronic infection

Abstract The present study describes natural genetic heterogeneity of hepatitis C virus (HCV) p7 protein, the ion channel that plays a critical role in assembly and release of HCV, within 299 variants isolated from serum specimens of 27 chronically infected patients, 12 of whom with human immunodefi...

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Bibliographic Details
Published in:Virology (New York, N.Y.) N.Y.), 2012-02, Vol.423 (1), p.30-37
Main Authors: Li, Hui, Atkins, Elizabeth, Bruckner, Joseph, McArdle, Susan, Qiu, Wan Chong, Thomassen, Lisa V, Scott, John, Shuhart, Margaret C, Livingston, Stephen, Townshend-Bulson, Lisa, McMahon, Brian J, Harris, Mark, Griffin, Stephen, Gretch, David R
Format: Article
Language:English
Subjects:
Adult
Amino Acid Sequence
Amino acid substitution
Amino acids
Channel gating
Chronic infection
Female
Fibrosis
Genetic diversity
Genetic Variation
Hepacivirus - chemistry
Hepacivirus - genetics
Hepacivirus - isolation & purification
Hepacivirus - metabolism
Hepatitis C virus
Hepatitis C, Chronic - virology
Human immunodeficiency virus
Humans
Infectious Disease
Ion channels
Liver diseases
Male
Middle Aged
Molecular Sequence Data
p7 protein
Sequence Alignment
Viral Proteins - chemistry
Viral Proteins - genetics
Viral Proteins - metabolism
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Summary:Abstract The present study describes natural genetic heterogeneity of hepatitis C virus (HCV) p7 protein, the ion channel that plays a critical role in assembly and release of HCV, within 299 variants isolated from serum specimens of 27 chronically infected patients, 12 of whom with human immunodeficiency virus (HIV) co-infection. Liver fibrosis stage was inversely correlated with p7 synonymous substitutions ( dS ) (p = 0.033), and indices of p7 genetic diversity were significantly higher in HIV-negative subjects compared to HIV-positive subjects ( dS , p = 0.005; non-synonymous substitutions ( dN ), p = 0.002; dN / dS ratio, p = 0.024; amino acid distances, p = 0.007). Six p7 genes with naturally occurring unique amino acid variations were selected for in vitro study. The variants demonstrated diversified functional heterogeneity in vitro, with one variant from a subject with severe liver disease displaying hyperactive ion channel function, as well as other variants presenting altered pH-activated channel gating activities.
ISSN:0042-6822
1096-0341
DOI:10.1016/j.virol.2011.11.011