Effects on apoptosis, cell cycle and transformation, and comparative aspects of EBV with other DNA tumor viruses

Abstract

The list of human viruses presently known to cause or to contribute to tumor development comprise four DNA viruses, Epstein–Barr virus, certain human papilloma virus subtypes, hepatitis B virus, and Kaposi sarcoma herpesvirus (HHV-8); and two RNA viruses, adult T-cell leukemia virus (HTLV-1) and hepatitis virus C. In addition, while HIV infection is not directly tumorigenic, it increases the incidence of certain tumors. The purpose of this chapter is to consider EBV and HHV-8 in relation to the known DNA tumor viruses, with particular focus on tumorigenicity. Viral strategy at the molecular level as a tumor risk factor Altered genes or environmental factors are usually considered as major risk factors for tumor development. However, the strategy of certain viruses may constitute a risk factor in itself. Tumor-associated viruses in humans have a survival strategy, like other viruses, aiming to maintain, replicate and propagate their genomes, but some features of this strategy entail a risk to initiate or favor tumor development under certain circumstances. This implies that only a small minority of the infected cells enter the pathway towards a malignant tumor and even fewer succeed. Three types of virus–host cell interactions may carry a risk Blocking of late viral functions or blocking the replicative cycle, by mutation or deletion of genetic material, e.g., due to the integration of the viral genome, as exemplified by HPV or adenovirus transformation in vitro. Infection of cells that are not fully permissive for viral replication, for species or tissue specific reasons. Permissiveness for the early but not the late functions of the viral cycle is particularly dangerous. The early viral proteins may exert continuous proliferation stimulating and/or apoptosis preventing effects. Infection of hamster or guinea pig cells with some of the human adenoviruses and SV40 infection of rodent cells may serve as examples. […]