R EVIEWS TRENDS IN MICROBIOLOGY 276 VOL. 6 NO. 7 JULY 1998 M embers of the gamma- herpesvirus subfamily are widespread in nature and infect a variety of mammalian species, including humans (Fig. 1). The major bio- logical characteristics of these viruses are (1) their ability to establish latent infections within lymphocytes, (2) their ability to induce lymphoproliferative disease and (3) their close as- sociation with a variety of both lymphoid and non-lymphoid cell tumours. Individual mem- bers of this subfamily are sub- divided into the 1-herpesviruses, typified by the B- lymphotropic Epstein–Barr virus (EBV) of humans and genetically related viruses of Old World primates 1 , and the 2-herpesviruses (rhadinoviruses), the prototype of which is the T-lymphotropic herpesvirus saimiri (HVS) of New World squirrel monkeys. Differences in the genomic organization and gene content of repre- sentative sequenced members of gammaherpesviruses form the basis for unambiguous assignment to either the 1 or 2 subgroupings (Fig. 2) because it is now clear that the latency tropism of 2-herpesviruses can be widespread and include both B and T cells. Indeed, the addition of the most recently identified human herpesvirus 8 (HHV-8; otherwise known as the Kaposi’s sarcoma-associated herpesvirus) to the 2 subgroup is based solely on genetic criteria and preceded detailed biological characterization of the virus 2 . Interest in the biology of the gammaherpesviruses stems largely from their association with a variety of malignancies. Thus, EBV is associated with Burkitt’s lymphoma, nasopharyngeal carcinoma and Hodgkin’s disease 3 , while HHV-8 genomes have been identified in nearly all Kaposi’s sarcoma tissues and several AIDS- related B-cell lymphomas 4 . The identification and bio- logical characterization of those gene products ex- pressed within tumour tissues is of key importance in understanding the mechanisms by which these viruses induce cellular proliferation, evade immune-mediated clearance and assure maintenance of the virus genome during latency. However, as exemplified by the best- studied gammaherpesvirus, EBV, differential patterns of gene expression are observed in tumours of different origin, and such expression patterns might be distinct from the minimal require- ments necessary for maintain- ing latency in the immunologi- cally intact host (for review, see Ref. 5). EBV and HHV-8 are species- specific viruses. In the case of EBV, studies of natural infec- tion have been largely restrict- ed to clinical presentation of disease. In the case of HHV-8, the nature of the primary in- fection and natural sites of virus latency remain unclear and, as for EBV, its restricted cell tropism, lack of fully per- missive cell lines and the absence of amenable animal model systems by which to study acute and latent in- fections have impeded research. For this reason, con- siderable interest has focused on the development of animal model systems to investigate the pathogenesis and immunology of gammaherpesvirus infection. One such candidate model system involves infection of laboratory mice with murine gammaherpesvirus 68 (MHV-68). This review will examine some of the key molecular, biological and immunological features of MHV-68 infection of laboratory mice and consider the poten- tial of this model system in the study of diverse patho- genic mechanisms associated with gammaherpesvirus infections. Origins of MHV-68 and characterization of the virus genome MHV-68 was originally isolated from the bank vole (Clethrionomys glariolus) in Slovakia and displays sero- logical and biological properties with other virus isolates recovered from wood mice (Apodemus flavicollis) trapped in the same locality 6,7 . These herpesviruses would therefore appear to be widespread among rodent populations in Northern Europe. MHV-68 is able to establish a productive infection in fibroblast and epithelial cell lines derived from several mammalian species, including humans 6,7 . Its initial classification as a member of the gammaherpesvirus subfamily came from sequence analyses of selected restriction frag- ments, which showed that several open reading frames (ORFs) displayed greater similarity to amino acid sequences encoded by the 2-herpesviruses, typified by Murine gammaherpesvirus 68 (MHV-68) is a naturally occurring herpesvirus of wild rodents and is genetically related to human herpesvirus 8 and Epstein–Barr virus. The ability of MHV-68 to establish acute and persistent infection within laboratory mice offers a unique opportunity to investigate immunological and virological aspects of gammaherpesvirus pathogenesis. J.P. Simas and S. Efstathiou* are in the Division of Virology, Dept of Pathology, University of Cambridge, Tennis Court Road, Cambridge, UK CB2 1QP. *tel: +44 1223 336919, fax: +44 1223 336926, e-mail: se@mole.bio.cam.ac.uk Murine gammaherpesvirus 68: a model for the study of gammaherpesvirus pathogenesis J. Pedro Simas and Stacey Efstathiou Copyright © 1998 Elsevier Science Ltd. All rights reserved. 0966 842X/98/$19.00 PII: S0966-842X(98)01306-7