Viruses and Cancer

Viruses are ubiquitous and are also the pathogenic agents that are most commonly associated with neoplastic transformation of cells of several organs in human beings – thereby causing cancer of epithelial cells (carcinomas) or cancer of mesenchymal cells (leukemias, lymphomas and sarcomas) depending on the type and location of the infected host cell. This review highlights the six major groups of viruses that have established aetiological association with cancer in human populations. The epidemiology and the processes through which these pathogens cause malignant transformation of the infected host cells are discussed – with particular emphasis on the evolving and changing natures of the diseases as they parallel changes in human behaviours. Also discussed is a brief overview of the current understanding of molecular pathology as they emerge with the advent of new technological capabilities for studying these processes at subcellular (genomic) levels. INTRODUCTION Viruses have notoriety for causing acute epidemic infections that may result in pandemics and global crisis within a short period of time. But also of an ever increasing need for attention due to the public health risk they constitute, are endemic diseases of viral origin and the associated malignancies. Viruses cause chronic infections that are endemic in many communities and such chronic infections have been shown to have aetiological associations with certain malignant disease processes that are also of endemic proportions in the affected communities. Considering the ubiquity of viruses and the high prevalence of viral infections worldwide, viruses are probably second only to tobacco abuse as the most common risk factor for developing cancer. In some cases, the development of cancer is directly related to the activities of the virus. In other cases, the virus remains dormant in host cells (carrier state) until factors such as immunosuppression and/or infection with other oncogenic viruses activates the oncogenic potentials of the virus in the carrier. This review highlights the interplay between environmental factors, host factors and viral factors that influence the oncogenic transformation of virus-infected host cells. 1. EPSTEIN BARR VIRUS 1:1 Epstein Barr Virus (EBV) Infection and The Immune System. Epstein Barr Virus (EBV) is a gamma herpesvirus that was first discovered in 1964 in SubSahara Africa by Epstein, Achong and Barr when they observed and reported the presence of herpesvirus-like particles in electron micrographs of cultured Burkitt lymphoma (Burkitt’s Lymphoma) cells (1). Shortly thereafter, higher titers of antibody to EBV antigens were reported in Burkitt’s Lymphoma patients (2), infectious mononucleosis and undifferentiated nasopharyngeal cancer (3,4). Since then, EBV has been shown to be an ubiquitous virus and the putative agent for an array of neoplastic lymphoproliferative disorders that include Hodgkin’s disease, non-Hodgkin’s B-cell lymphomas, immunosuppression-associated lymphomas, some T-cell lymphomas; and a subset of gastric adenocarcinoma. All these tumours have been shown to contain EBV genome and EBV-coded latent genes which play active roles in the malignant transformation of infected cells. EBV is a linear double-stranded DNA gammaherpesvirus with global presence. It infects about 95% of adult populations in every part of the world and has a life-long persistence in infected individuals. The primary infection may be asymptomatic and occur early in life or it may occur later during pubertal years or adulthood as infectious mononucleosis (5,6). Although the virus can infect epithelial cells, T-lymphocytes and B-lymphocytes, the latter are the preferred target cells (7). EBV is orally transmitted and the oropharynx is the primary site of infection and also the site for virus replication; hence, the spread of the virus through the saliva of infected persons (8,9). During the primary infection of Bcells, there is an initial short-lived but critical