E2 Quasispecies specificity of hepatitis C virus association with allografts immediately after liver transplantation

Michael G. Hughes, Christine K. Rudy, Tae W. Chong, Robert L. Smith, Heather L. Evans, Julia C. Iezzoni, Robert G. Sawyer, Timothy L. Pruett

Research output: Contribution to journalArticle

26 Citations (Scopus)

Abstract

It is unknown whether all hepatitis C virus (HCV) quasispecies variants found within patient serum have equal capacity to associate with the liver after transplantation; however, in vitro models of HCV infection suggest that variations in the hypervariable region 1 (HVR1) of the second envelope protein (E2) may be important in infectivity. The hypothesis of the current study is that the two hypervariable regions (HVR1 and HVR2) within E2 are important in the initial virus-liver interaction, and, therefore, certain HCV quasispecies variants will be isolated from the liver after reperfusion. In 8 patients with endstage liver disease secondary to HCV infection, HCV envelope quasispecies were determined from intraoperative serum samples obtained before the anhepatic phase of transplantation and from liver biopsies 1.5 to 2.5 hours after the transplanted liver was perfused. Explanted (native) liver biopsies were taken as a control. Sequence analysis was performed on clones of specific HCV reverse transcriptase-polymerase chain reaction products spanning HVR1 and HVR2 of the E2 protein. HVR1 was more variable than HVR2 for all samples. Quasispecies isolated from postperfusion liver differed more from serum than did explanted liver quasispecies at HVR1 (P = 0.03) but not at HVR2 (P = 0.2). Comparison of HVR1 sequences from postperfusion liver versus serum revealed significantly less HVR1 genetic complexity and diversity (P = 0.02 and P = 0.04, respectively). Immediately after transplantation but before actual infection, liver allografts select out from the infecting serum inoculum a less heterogeneous, more closely related population of quasispecies variants.

Original languageEnglish (US)
Pages (from-to)208-216
Number of pages9
JournalLiver Transplantation
Volume10
Issue number2
DOIs
StatePublished - Feb 2004

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Hepacivirus
Liver Transplantation
Allografts
Liver
Serum
Virus Diseases
Biopsy
Reverse Transcriptase Polymerase Chain Reaction
Reperfusion
Sequence Analysis
Liver Diseases
Proteins
Clone Cells
Transplantation
Viruses
Infection
Population

ASJC Scopus subject areas

  • Surgery
  • Transplantation

Cite this

Hughes, M. G., Rudy, C. K., Chong, T. W., Smith, R. L., Evans, H. L., Iezzoni, J. C., ... Pruett, T. L. (2004). E2 Quasispecies specificity of hepatitis C virus association with allografts immediately after liver transplantation. Liver Transplantation, 10(2), 208-216. https://doi.org/10.1002/lt.20060

E2 Quasispecies specificity of hepatitis C virus association with allografts immediately after liver transplantation. / Hughes, Michael G.; Rudy, Christine K.; Chong, Tae W.; Smith, Robert L.; Evans, Heather L.; Iezzoni, Julia C.; Sawyer, Robert G.; Pruett, Timothy L.

In: Liver Transplantation, Vol. 10, No. 2, 02.2004, p. 208-216.

Research output: Contribution to journalArticle

Hughes, MG, Rudy, CK, Chong, TW, Smith, RL, Evans, HL, Iezzoni, JC, Sawyer, RG & Pruett, TL 2004, 'E2 Quasispecies specificity of hepatitis C virus association with allografts immediately after liver transplantation', Liver Transplantation, vol. 10, no. 2, pp. 208-216. https://doi.org/10.1002/lt.20060
Hughes, Michael G. ; Rudy, Christine K. ; Chong, Tae W. ; Smith, Robert L. ; Evans, Heather L. ; Iezzoni, Julia C. ; Sawyer, Robert G. ; Pruett, Timothy L. / E2 Quasispecies specificity of hepatitis C virus association with allografts immediately after liver transplantation. In: Liver Transplantation. 2004 ; Vol. 10, No. 2. pp. 208-216.
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