In vivo models for Epstein-Barr virus (EBV)-associated B cell lymphoproliferative disease (BLPD)

Citation
I. Johannessen et Dh. Crawford, In vivo models for Epstein-Barr virus (EBV)-associated B cell lymphoproliferative disease (BLPD), REV MED VIR, 9(4), 1999, pp. 263-277
Citations number
141
Categorie Soggetti
Microbiology
Journal title
REVIEWS IN MEDICAL VIROLOGY
ISSN journal
10529276 → ACNP
Volume
9
Issue
4
Year of publication
1999
Pages
263 - 277
Database
ISI
SICI code
1052-9276(199910/12)9:4<263:IVMFEV>2.0.ZU;2-G
Abstract
EBV infects B lymphocytes in vivo and establishes a life-long persistent in fection in the host. The latent infection is controlled by EBV-specific MHC class I-restricted CTL. Immunosuppression reduces CTL activity, and this f acilitates outgrowth of EBV+ve B cell lymphoproliferative disease (BLPD). B LPD are aggressive lesions with high mortality. This review presents some k ey facets in the development of EBV-associated BLPD and in vivo studies on its pathogenesis. The animal models used to date include the common marmose t (Callithrix jacchtas), the cottontop tamarin (Saguinus oedipus oedipus), rhesus monkey, murine herpesvirus 68 (MHV68), and the severe combined immun odeficient (scid) mouse, each of which has been used to address particular aspects of EBV biology and BLPD development. Scid mice inoculated i.p. with PBMC from EBV-seropositive individuals develop EBV+ve BLPD-like tumours. T hus this small animal model (hu-PBMC-scid) is currently used by many labora tories to investigate EBV-associated diseases. We and others have studied B LPD pathogenesis in the hu-PBMC-scid model and shown that EBV + ve B cells on their own do not give rise to rumours in this model without inclusion of autologous T cell subsets in the inoculum. Based on the findings that (1) established rumours do not contain T cells and (2) tumour cells express a v ariety of B cell growth factors, a stepwise model of lymphomagenesis in the scid mouse model can be defined. Additionally, the hu-PBMC-scid model can be used to assess novel therapeutic regimes against BLPD before introductio n into a clinical setting. Copyright (C) 1999 John Wiley & Sons, Ltd.