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Hepatitis C in human immunodeficiency virus-coinfected patients: increased variability in the hypervariable envelope
K E Sherman1, C Andreatta, J O'Brien
1Department of Medicine and Pathology, University of Cincinnati Medical Center, OH, USA.
Hepatology (Baltimore, Md.)
|April 1, 1996
Summary
Hepatitis C virus (HCV) and human immunodeficiency virus (HIV) coinfection leads to increased HCV E2/NS1 hypervariable region variability. This viral evolution may contribute to interferon resistance in coinfected patients.
Area of Science:
- Virology
- Immunology
- Genetics
Background:
- Hepatitis C virus (HCV) and human immunodeficiency virus (HIV) coinfection is common.
- Understanding HCV genetic variability is crucial for treatment efficacy, particularly in coinfected individuals.
Purpose of the Study:
- To investigate nucleotide sequence variability in the HCV E2/NS1 hypervariable region in patients coinfected with HCV and HIV.
- To compare this variability with that observed in patients infected solely with HCV.
Main Methods:
- Sequencing of 91 clones from 10 HCV/HIV coinfected patients and 53 clones from 7 HCV-only patients.
- Analysis focused on the E2/NS1 hypervariable region (amino acids 384-414).
- Evaluation of synonymous/nonsynonymous amino acid changes and prediction of high-antigenicity sites.
Main Results:
- Significantly increased HCV RNA variability in coinfected patients compared to HCV-only patients (P < .05).
- Highest variability observed at specific amino acid sites (386, 397, 400, 402, 405, 407, 414).
- Nonsynonymous variations altered putative antigenic sites, with unique antigenic domains more frequent in coinfected individuals.
Conclusions:
- HCV/HIV coinfection promotes the accumulation of HCV envelope variants.
- Increased viral diversity may be linked to impaired viral clearance and interferon (IFN) resistance in coinfected patients.