title: HCV infection of the transplanted liver: changing CD81 and HVR1 variants immediately after liver transplantation.
abstract: The second envelope protein at hypervariable region 1 (HVR1) has been implicated in contributing to hepatitis C virus (HCV)-host cell interactions and CD81 (a multifunctional protein) has been demonstrated to act as a cell surface receptor for HCV and may interact directly with HVR1. The purpose of the current study was to determine if certain HVR1 quasispecies variants more effectively associate with and infect allografts after liver transplantation than other HVR1 variants and whether CD81 receptor expression changes after transplantation. Blood and allograft samples were obtained from the peritransplant period in seven patients. Clones of RT-PCR product were directly sequenced to identify HVR1 quasispecies variants. Explanted liver and serial allograft biopsies in recipients with HCV were examined by immunohistochemistry (IHC) for CD81 expression. Examination of HVR1 sequences demonstrated that only a fraction of the quasispecies variants recovered from each patient's blood sampled immediately prior to transplantation associated with and infected the allografts. Genetic diversity at HVR1 decreased with reperfusion but did not significantly decrease with infection. Expression of CD81 varied during the immediate post-transplant period. In conclusion, HVR1 quasispecies variants differentially associate with, and infect allografts, after liver transplantation. Additionally, allografts express variable amounts of CD81 after transplantation.
authors.affiliation: Department of Surgery, Surgical Infectious Disease Laboratory, University of Virginia, Charlottesville, Virginia, USA. mgh6a@virginia.edu
authors.forename: Michael G
authors.initials: MG
authors.lastname: Hughes
authors.forename: Tae W
authors.initials: TW
authors.lastname: Chong
authors.forename: Robert L
authors.initials: RL
authors.lastname: Smith
authors.forename: Heather L
authors.initials: HL
authors.lastname: Evans
authors.forename: Julia C
authors.initials: JC
authors.lastname: Iezzoni
authors.forename: Robert G
authors.initials: RG
authors.lastname: Sawyer
authors.forename: Christine K
authors.initials: CK
authors.lastname: Rudy
authors.forename: Timothy L
authors.initials: TL
authors.lastname: Pruett
mesh_terms: D000595:Amino Acid Sequence; D015703:Antigens, CD / Q000096:biosynthesis*; D001706:Biopsy; D002462:Cell Membrane / Q000378:metabolism; D003001:Cloning, Molecular; D014644:Genetic Variation; D016174:Hepacivirus / Q000378:metabolism*; D006526:Hepatitis C / Q000473:pathology*; D018937:Hepatitis C Antibodies / Q000737:chemistry; D006801:Humans; D007150:Immunohistochemistry; D008099:Liver / Q000821:virology*; D016031:Liver Transplantation / Q000009:adverse effects* / Q000379:methods*; D008969:Molecular Sequence Data; D011183:Postoperative Complications; D012313:RNA / Q000378:metabolism; D012367:RNA, Viral / Q000032:analysis; D012008:Recurrence; D015424:Reperfusion; D020133:Reverse Transcriptase Polymerase Chain Reaction; D017422:Sequence Analysis, DNA; D017386:Sequence Homology, Amino Acid; D060225:Tetraspanin 28; D013997:Time Factors; D014184:Transplantation, Homologous / Q000379:methods; D014764:Viral Proteins / Q000096:biosynthesis*
chemical_list: D015703:Antigens, CD; C554798:CD81 protein, human; C400562:HVR1 protein, Hepatitis C virus; D018937:Hepatitis C Antibodies; D012367:RNA, Viral; D060225:Tetraspanin 28; D014764:Viral Proteins; D012313:RNA