Gammaherpesviruses of New World primates

Excerpt

Numerous Gamma-herpesviruses, a large subfamily of the herpes group, have limited pathogenic potential upon primary infection of their natural host. They are most relevant however as tumor viruses of the hematopoietic system and form an important chapter of viral oncology. The prototype of the genus lymphocryptovirus (γ1-herpesvirus), Epstein-Barr Virus (EBV), was the first clearly identified human herpesvirus. EBV causes lymphomas of B-cell origin and other lymphoproliferative syndromes, nasopharyngeal carcinomas and, possibly, gastric cancer. The second known genus of gamma-herpesviruses, rhadinoviruses or γ2-herpesviruses, is biologically and molecularly distinct. The prototypic members of this group, termed Herpesvirus (H.) saimiri (HVS) and H. ateles (HVA), were detected as T-lymphotropic tumor viruses in neotropical primates and raised primary interest from the fact that they cause fulminant T-cell lymphomas in numerous primates as well as in rabbits, although no exact correlates of these tumors exist in human pathology. This led to the identification of novel viral membrane-associated T-cell oncoproteins, termed Stp and Tip. These are small adaptor molecules that efficiently act on T-lymphocyte signaling. The viruses have been used as expression vectors in T-lymphocytes and allow to study mechanisms of episomal persistence in components of the T-cell system. Later on it became clear that certain strains of HVS can transform human T-lymphocytes to continuous growth in an antigen- and mitogen-independent fashion, providing for the first time a reliable means of human T-lymphocyte immortalization in cell culture. Additional interest in the γ2-herpesviruses arose when the Kaposi-sarcoma-associated Human Herpesvirus 8 (KSHV/HHV8) was identified as the first human pathogenic rhadinovirus. However, in view of the complex biology of Kaposi’s Sarcoma or other neoplastic diseases such as body cavity-based B-cell lymphomas and multifocal Castleman’s Disease, it is by far less clear which KSHV/HHV8 genes encode the relevant oncoproteins of KSHV/HHV-8. In this chapter, we wanted to focus mostly on the basic biology and gene expression profiles of HVS and HVA, on the viral mechanisms of oncogenic transformation, and possible applications of these viruses as T-cell vectors and in cell-based immunotherapy.