Herpesvirus saimiri

Herpesvirus saimiri (saimiriine herpesvirus 2) is the classical prototype o f the gamma (2)-herpesviruses or rhadinoviruses, which also contains a huma n member, the Kaposi's sarcoma-associated herpesvirus. The T-lymphotropic H erpesvirus saimiri establishes specific replicative and persistent conditio ns in different primate host species. Virtually all squirrel monkeys (Saimi ri sciureus) are persistently infected with this virus. In its natural host , the virus does not cause disease, whereas it induces fatal acute T-cell l ymphoma in other monkey species after experimental infection. The virus can be isolated by cocultivation of permissive epithelial cells with periphera l blood cells from naturally infected squirrel monkeys and from susceptible New World monkeys during the virus-induced disease. Tumour-derived and in vitro-transformed T-cell lines from New World monkeys release virus particl es. Herpesvirus ateles is a closely related virus of spider monkeys (Ateles spp.) and has similar pathogenic properties to Herpesvirus saimiri in othe r New World primate species. Similar to other rhadinoviruses, the genome of Herpesvirus saimiri harbours a series of virus genes with pronounced homology to cellular counterparts including a D-type cyclin, a G-protein coupled receptor, an interleukin-17, a superantigen homologue, and several inhibitors: of the complement cascad e and of different apoptosis pathways. Preserved function has been demonstr ated for most of the homologues of cellular proteins. These viral functions are capability of the virus. However, they are considered relevant for the pathogenic persistence of Herpesvirus saimiri in its natural host. A termi nal region of the non-repetitive coding part of the virus genome is essenti al for pathogenicity and T-cell transformation. Based on the pathogenic phe notypes and the different alleles of this variable region, the virus strain s have been assigned to three subgroups, termed A, B and C. In the highly o ncogenic subgroup C strains, the two virus genes stpC and tip are transcrib ed from one bicistronic mRNA and are essential for transformation and leuka emia induction. stpC fulfils the typical criteria of an oncogene; its produ ct interacts with Ras and tumour necrosis factor-associated factors and ind uces mitogen-activated protein kinase and nuclear factor kappa B activation . Tip interacts with the RNA transport factor Tap, with signal transduction and activation of transcription factors, and with the T-cellular tyrosine kinase Lck, which is activated by this interaction and phosphorylates Tip a s a substrate. It is of particular interest that certain subgroup C virus strains such as C488 are capable of transforming human T lymphocytes to stable growth in cu lture. The transformed human T cells harbour multiple copies of tile viral genome in the form of stable, non-integrated episomes. The cells express on ly a few virus genes and do not produce virus particles. The transformed ce lls maintain the antigen specificity and many other essential functions of their parental T-cell clones. Based on the prescribed functional phenotype of the transformed T cells, Herpesvirus saimiri provides useful tools for T -cell immunology; for gene transfer and possibly also for experimental adop tive immunotherapy.