10 Oncogenesis by Herpesviruses

Abstract

I. INTRODUCTION
The herpesviruses are a diverse group of animal viruses that share common structural features and common intracellular replication schemes (for review, see Roizman and Batterson 1985). Herpesviruses have a complex core consisting of linear, double-strand DNA (100–250 kbp) wrapped around a protein toroid, a proteinaceous nucleocapsid shell, and an outer protein phospholipid bilayer membrane with glycoprotein spikes. Almost every animal species has at least one herpesvirus that is highly prevalent in that species and rarely, if ever, infects heterologous species. Herpesviruses vary widely in oncogenicity. Epstein-Barr virus (EBV), a human herpesvirus, and Marek’s disease virus (MDV), a chicken herpesvirus, are important causes of natural malignancies. EBV has been the dominant focus of oncogenic herpesvirus research and is therefore considered in greatest depth throughout this review. Another herpesvirus, herpesvirus saimiri (HVS), does not cause naturally occurring malignancies but efficiently induces tumors in heterologous species and transforms cells in vitro. Most herpesviruses, however, have little obvious direct oncogenic activity.

A. Properties of Herpesviruses Relevant to Their Oncogenicity
Despite the wide variation in oncogenicity among herpesviruses, there are themes in herpesvirus oncogenicity that derive from the common properties of the herpesvirus class. Herpesviruses have more than 50 genes. They replicate their DNA within the cell nucleus and assemble into nucleocapsids at the nuclear periphery. The cell nucleus is profoundly altered by virus replication. Nucleoli are disaggregated. Chromatin becomes marginated to the nuclear periphery. Cell DNA transcription and replication cease as virus DNA transcription and replication proceed. Nucleocapsids are initially enveloped...