A longitudinal analysis of T-cell epitope-coding regions of hepatitis C virus after liver transplantation

Hugo R. Rosen, Gail Marousek, Sunwen Chou

Research output: Contribution to journalArticle

12 Citations (Scopus)

Abstract

Background. Hepatitis C virus (HCV)-related liver failure is the single leading indication for orthotopic liver transplantation (OLT) worldwide. The mechanisms that underlie the observed differences in natural history of HCV recurrence remain poorly understood. We have previously demonstrated that differential T-cell responses correlate with histologic severity after OLT. We hypothesized that amino acid substitutions within critical T-cell epitopes could lead to increased severity of HCV disease. Methods. We determined the peptide sequences from sequential serum-derived viral RNA by reverse transcription and direct polymerase chain reaction sequence analysis from 32 HCV genotype 1-infected patients with well-characterized outcomes after liver transplantation. Serum samples were analyzed for HCV sequence the day of OLT and at least one time point post-OLT. To construct evolutionary relationships among the different patient samples, phylogenetic analyses of core and NS3 sequences were performed using a matrix fed into a neighbor-joining tree algorithm. Results. The phylogenetic analyses revealed remarkable conservation within a given individual and no significant differences when comparing patients with severe versus mild recurrence. Accordingly, the synonymous mutation rate was consistently greater than the nonsynonymous substitution rate. The nine epitopic regions analyzed were also preserved so that, with the exception of one patient with mild recurrence, none of the patients demonstrated a shift in viral peptide sequence. Conclusions. HCV core and NS3 viral peptide sequences are identical before and after OLT in most patients, suggesting that the prevalent sequence is preserved in most cases, and viral variants are competent to establish infection after OLT. Although these results do not support viral mutation as a dominant pathogenic mechanism after OLT, other viral regions need to be analyzed.

Original languageEnglish (US)
Pages (from-to)209-216
Number of pages8
JournalTransplantation
Volume74
Issue number2
StatePublished - Jul 27 2002
Externally publishedYes

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T-Lymphocyte Epitopes
Hepacivirus
Liver Transplantation
Recurrence
Peptides
Liver Failure
Viral RNA
Virus Diseases
Mutation Rate
Amino Acid Substitution
Natural History
Serum
Reverse Transcription
Sequence Analysis
Genotype
T-Lymphocytes
Polymerase Chain Reaction
Mutation
Infection

ASJC Scopus subject areas

  • Transplantation
  • Immunology

Cite this

A longitudinal analysis of T-cell epitope-coding regions of hepatitis C virus after liver transplantation. / Rosen, Hugo R.; Marousek, Gail; Chou, Sunwen.

In: Transplantation, Vol. 74, No. 2, 27.07.2002, p. 209-216.

Research output: Contribution to journalArticle

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