The role of EBV in post-transplant malignancies: a review
- 1The University of Edinburgh, Medical School, Department of Medical Microbiology, Teviot Place, Edinburgh EH8 9AG, UK
- Professor Crawford email:
- Accepted 17 August 1999
Post-transplant lymphoproliferative disorder (PTLD) is a rare but frequently fatal complication of iatrogenic immunosuppression. PTLD encompasses a spectrum of B cell lymphoproliferations ranging from reactive plasmacytic hyperplasia to monomorphic B cell lymphoma.1 The tumours are almost always associated with Epstein-Barr Virus (EBV), and similar lymphoproliferative disorders also occur in other congenital and acquired immunodeficiency states.2 These malignancies reflect an imbalance in the normal control of EBV infection, although the virus is also linked to a subset of Hodgkin's disease and T cell lymphomas in apparently immunocompetent individuals.3–5 Other EBV associated tumours occurring in particular areas of the world include Burkitt's lymphoma in equatorial Africa and nasopharyngeal carcinoma in South East Asia.2 This review discusses the biology of EBV infection in the normal and immunocompromised host and the risk factors and pathogenesis of EBV associated PTLD.
EBV is an enveloped herpesvirus with a 172 kb double stranded DNA genome.2 A defining feature of herpesviruses is their ability to maintain a latent infection with the virus genome retained in host cells without production of infectious virions. EBV targets B lymphocytes through the CD21 receptor and establishes a latent infection both in vivo and in vitro.
EBV INFECTION IN VITRO
In vitro infection of B lymphocytes with EBV results in the establishment of an immortalised B lymphoblastoid cell line in which the majority of cells contain a non-replicating episomal form of the EBV genome and only a small proportion of cells contain replicating virus. Lymphoblastoid cell lines express a panel of EBV encoded latent antigens which comprise six nuclear proteins (Epstein-Barr nuclear antigens (EBNA)1, -2, -3A, -3B, -3C, and leader protein (LP)) and three latent membrane antigens (LMP1, -2A, and -2B). Abundantly expressed small non-polyadenylated RNAs termed Epstein-Barr virus early RNA (EBER) 1 and 2 are transcribed but not translated, and …