Human herpesvirus-6 infection is associated with adhesion molecule induction and lymphocyte infiltration in liver allografts

Background/Aims: Human herpesvirus-6 (HHV-6) infection has been recently described in liver transplants. HHV-6 may infect the transplant and cause graft dysfunction. Some association between HHV-6 and rejection has also been recorded. We have now investigated the possible involvement of HHV-6 in the intragraft immunological processes, adhesion molecules induction and lymphocyte activation. Methods: HHV-6 was detected in liver biopsies of 19 patients transplanted in the period from 1996 to 2000. Patients with other infections or rejection were excluded from the study. Finally, 19 biopsies of eight allografts with pure HHV-6 infection were available. Adhesion molecules (ICAM-1, VCAM-1, ELAM-1) and their ligands (LFA-1, VLA-4, sLeX) and lymphoid activation markers (MHC class II, IL-2R) were demonstrated in liver biopsies by immunohistochemistry. Five biopsies from patients with normal graft function and without rejection or infection were used as controls for immune staining, and ten biopsies with acute rejection but without infection were used as positive controls. Results: Biopsy histology demonstrated mild to moderate lymphocyte infiltration associated with HHV-6 infection. HHV-6 significantly (P≤0.05) increased the vascular expression of ICAM-1 and VCAM-1, and the number of graft infiltrating lymphocytes positive for LFA-1, VLA-4 and class II antigens. A total of 3/8 grafts developed chronic rejection. Conclusions: HHV-6 infection increased adhesion molecule expression and lymphocyte infiltration in liver allografts.