VIRAL ONCOGENESIS PREFACE

In recent years, investigations with different tumour virus models gave important contributions and led to the acquisition of significant advances in many biomedical fields. It is worth reminding, as examples, that DNA tumour viruses such as SV40 allowed the discovery of the p53 tumour suppressor gene, whereas studying the adenoviruses, scientists found out that eukaryotic genes are split in exons and introns, and a new mechanism of RNA maturation, termed splicing, was revealed. Other important achievements, such as the discovery of the reverse transcriptase and oncogenes were obtained studying the oncogenic retroviruses. At their infancy, also the molecular genetics and genetic engineering allowed the production of eukaryotic vectors employing the nucleic acids of different tumour viruses. DNA and RNA tumour viruses are important tools to study the fine mechanisms of cellular transformation and to understand how they induce in vivo the onset of malignancies. In approximately one century of active research in viral oncology, scientists discovered that tumour viruses, as carcinogenic agents, may directly induce cell transformation or are important co-factors in tumourigenesis. In this book, distinguished scientists contributed with eight different chapters where the mechanisms of cell transformation operated by DNA and RNA tumour viruses are described. The first three chapters are dedicated to the polyomaviruses, named BK, JC and SV40. These small DNA tumour viruses have been studied as oncogenic agents since their isolation in the 1960, SV40 and 1971, BK and JC. Many reports indicate that the BK, JC and SV40 polyomaviruses are able to transform cultured human cells, and are associated with specific human tumours. However, their involvement in the onset of human tumours remains to be elucidated. In the eighties the human papillomaviruses (HPV) were linked to the onset of the ano-genital tumours in humans. Since then, a great amount of data have been accumulated in this topic, and now after more than 20 years of research in this field, the scientific community agrees that oncogenic papillomavirus types are directly involved in the development of anal and genital tumours in human. The large amount of results collected on the oncogenic papillomaviruses helped the scientists to develop specific anti-tumor vaccines. Some of them are already tested in clinical trials and very likely, in a few years, vaccines against oncogenic papillomaviruses and HPV-induced tumours will be available in the market. Human adenoviruses are composed of both transforming and tumourigenic types. It is important to remind that no association was revealed between the oncogenic adenovirus types and human tumours. However, the adenoviruses as models of study in oncogenesis allowed to understand how the oncogenic types are able to circumvent the presence of an active immune-response in vivo. Human herpesviruses, such as the Epstein-Barr virus (EBV) and the human herpesvirus 8 are related to specific tumours. It is well established that EBV is ubiquitous in humans, but many results suggest that EBV is involved in human oncogenesis as co-factor. EBV during latency induces the cells to proliferate and gives to them the ability to escape the immune responses. Important contributions in oncogenesis were made possible by studying the oncogenic herpesviruses, such as the discovery of the mechanism of induction of growth factors and cytokines in infected cells. Chronic infection with hepatitis B virus (HBV) is the main cause of the hepatocellular carcinoma (HCC) in human. However, in recent years the advent of the vaccine against HBV dramatically reduced this viral infection with the concomitant decrease of HCC incidence. It has been shown that also the hepatitis C virus (HCV), a non-retroviral oncogenic RNA+ virus, infection is associated with the HCC in human. The lack of models did not allow so far to understand the mechanisms of cell transformation employed by HCV in the liver. It is well known that the oncogenic retroviruses were the first biological agents, discovered almost a century ago, with ability to induce tumours in vivo. After the discovery of avian oncogenic retroviruses many other animal retroviruses were detected in their natural hosts. In the last 25 years oncogenic retroviruses were also isolated in humans. The last chapter is dedicated to the human T-cell leukemia virus type-I (HTLV-I), which is considered a sort of prototype for the group of RNA tumour viruses. Many significant advances obtained studying the HTLV-1 model helped also to understand how HIV multiplies in human and which targets should be use in AIDS therapy. The book “Viral Oncogenesis” is addressed to those readers who wish to have an overview of how different tumour viruses may transform human and animal cells, during the multistep process of the cancerogenesis. Mauro Tognon