The Papovaviridae

It has been more than twenty years since the isolation of polyoma virus and SV40, and the reports that they could produce tumors in animals and transformation of cells in culture. What was startling was that these biologic properties are associated with viruses that contain genetic in formation that is able to code for only five or six proteins. Since that time, investigations with these viruses have been in four principal areas. One major area of study has been on cells transformed by viruses that show altered growth properties and specify new viral and cellular proteins. Transformation studies have focused on the tumor (T) antigens that are specified by the virus and are required to initiate and to maintain the transformed state. Current studies on transformation are summarized in Chapter 4. The second broad area of investigation concerns replication of viruses during a lytic cycle of infection. T-antigens that are the hallmark of transformed cells are also expressed in cells that are lytically infected and are required for viral DNA replication and also function to alter rates of transcription of the early and late viral genes. Except for T-antigen, virus replication depends on the cellular enzymatic machinery and so the description of viral macromolecular synthesis has provided valuable insights into the cellular biosynthetic pathways. These studies are described in Chapters 1-3. The studies that have medical relevance concern JC and BK viruses and there is evidence of widespread exposure of human populations to these agents.

It has been more than twenty years since the isolation of polyoma virus and SV40, and the reports that they could produce tumors in animals and transformation of cells in culture. What was startling was that these biologic properties are associated with viruses that contain genetic in formation that is able to code for only five or six proteins. Since that time, investigations with these viruses have been in four principal areas. One major area of study has been on cells transformed by viruses that show altered growth properties and specify new viral and cellular proteins. Transformation studies have focused on the tumor (T) antigens that are specified by the virus and are required to initiate and to maintain the transformed state. Current studies on transformation are summarized in Chapter 4. The second broad area of investigation concerns replication of viruses during a lytic cycle of infection. T-antigens that are the hallmark of transformed cells are also expressed in cells that are lytically infected and are required for viral DNA replication and also function to alter rates of transcription of the early and late viral genes. Except for T-antigen, virus replication depends on the cellular enzymatic machinery and so the description of viral macromolecular synthesis has provided valuable insights into the cellular biosynthetic pathways. These studies are described in Chapters 1-3. The studies that have medical relevance concern JC and BK viruses and there is evidence of widespread exposure of human populations to these agents.

This ninetieth volume of the IARC Monographs on the Evaluation of Carcinogenic Risks to Humansconsiders human papillomaviruses (HPVs) which were evaluated by a previous Working Group (IARC, 1995). The monograph in the present volume incorporates new data that have become available during the past decade. HPVs represent the most common infectious agents that are transmitted sexually throughout the world; the major risk factors are behaviors associated with sexual activity. Although most infections are asymptomatic and are cleared within a period of 2 years, genital HPV infection can lead to clinical disease, including anogenital warts, cervical neoplasia, cervical cancer and other anogenital cancers. The risk for persistence of infection and progression of the more than 40 genital HPV types to grade 3 cervical intraepithelial neoplasia (CIN3) and cancer differs widely. Persistent infection with carcinogenic HPVs occurs in virtually all cases of cervical cancer. Previous evaluations of HPVs have classified types 16 and 18 as carcinogenic to humans (group 1), types 31 and 33 as probably carcinogenic to humans (Group 2A) and some types other than 16, 18, 31 and 33 as possibly carcinogenic to humans (Group 2B). At that time, the evaluation of types 16 and 18 was based on the strong association between infection with these HPVs and cervical cancer. For types 31 and 33, the association was less strong. The new epidemiological data reviewed in the present volume strongly support and further confirm the previous evaluation of types 16 and 18, and provide new evidence for other HPVs. This information, which includes strong evidence of carcinogenicity at sites other than the cervix, supports new evaluations for several other HPV types in addition to those mentioned above. Since the Working Group was convened in 2005, important innovations in HPV prophylaxis have occurred and these needed to be included in this volume. To date two prophylactic vaccines have been developed and used in large multicentric trials. This prophylactic vaccination is expected to reduce the incidence of HPV-related genital diseases. However, the benefits of prophylactic vaccines in a broad public health perspective will be achieved only if such vaccines can be provided to those groups of women for whom access to cervical cancer screening services is most problematic. Therefore, the development of second-generation vaccines that are expected to be cheaper, easier to deliver and to provide T-cell response against pre-existing HPV infections is highly desirable.

The all new Concepts in Viral Pathogenesis III contains the widely praised format of presenting up-to-date information in pithy, easily read "mini-review" style and complements previous editions with contributions by leading international authorities on structure-function relationships, gene regulation, cell biology of viral infections, transgenic mice, expression of viral genes, retroviruses, and evolving concepts in viral diseases. Taken together, Volume I, II and III of Concepts in Viral Pathogenesis contain 145 unique chapters each representing the latest thinking in important areas of virology by the foremost investigators in the field. Clinicians, laboratory scientists, students, and others seeking authoritative overviews of current knowledge on the mechanism of viral diseases will welcome this valuable resource.

This volume gives special reference to papillomaviruses in benign precursor lesions related to genital tumors, plus it provides a basis for a more reproducible evaluation of the pathology of papillomavirus-induced lesions. It deals with the molecular biology of papillomaviruses as it relates to our understanding of viral cell transformation and malignant conversion. Written in a comprehensive, easy-to-read format, this book covers points of medical interest such as diagnosis, therapy, and prospects for vaccination. This fascinating text provides current, state-of-the-art practices for immediate and future medical research. Virologists, microbiologists, and cancer researchers will find this work interesting and resourceful.