Human Papillomavirus (HPV)
(adapted from M. Saveria Campo in Papillomavirus Research)
Papillomaviruses: (PVs) are oncogenic DNA tumour viruses. They infect cutaneous and mucous epithelia in a variety of animals, including humans, through cuts or abrasions, and induce papillomas or warts, which generally regress without eliciting any serious clinical problems in the host, but can occasionally persist and progress to malignancy. There are upward of 300 distinct types of PVs, including probably 200 different types of human papillomavirus (HPV), and it is likely that more types will be found, particularly in animals.
Despite their remarkable heterogeneity, all PVs have a very similar genomic organisation. The viral genome is a double stranded circular DNA molecule of approximately 8 kilobases (kb), which can be divided into three regions: the E region coding for early proteins (E1-E7) responsible for the pathogenicity of the virus; the L region coding for late structural proteins (L1, L2), and a non-coding region which contains the cis-elements necessary for replication and transcription of the viral genome. All the known genes are encoded in one DNA stand and transcription is unidirectional (Figure 1, Introduction).
The life cycle of the virus is tightly coupled with the differentiation process of the epithelial cell: the virus infects the basal keratinocytes, expresses part of its genes in the basal and suprabasal layers, replicates its genome in the differentiating spinous and granular layers, expresses its structural genes and packages its DNA in the squamous layers (there are exception to this general rule, which will be discussed in later chapters), and new infectious virus is finally released with the keratinised squames. During its whole life cycle, the PV genome persists in the infected cell as an episome.
PV does not always go through its full productive life cycle. Occasionally benign tumours persist and may progress to squamous cell carcinoma. From the viral "point of view", neoplastic progression is an accident; cell transformation is a dead-end process for the virus as the transformed cell is no longer permissive for virion production; the viral genome is either incorporated into the cellular genome, as in anogenital squamous cell carcinoma in human; maintained as an extrachromosomal element which replicates in synchrony with the cell cycle, as in urothelial cancers in cattle, or may even be lost by the transformed cells, as in squamous cell carcinomas of the upper gastrointestinal tract in cattle and non-melanoma skin cancer in humans.
One important feature of PVs is their strict species-specificity: even in experimental conditions, PVs do not infect any other host than their natural one. The only known case of naturally occurring cross-species infection is the infection of horses and other equids by bovine papillomavirus (BPV) type 1 and type 2. Given the apparently insurmountable problem of species-specificity, no animal model of HPV infection exists and papillomavirologists have had in the past to rely for direct experimentation on animal papillomavirus systems. The recent advent of organotypic raft cultures, virus-like particles (VLPs) and transgenic mice has revolutionised the PV field revealing new facets of HPV virion structure, life cycle, immunology and oncogenicity.
This book attempts to cover all aspects of PV natural history, from the recognition of PV as a cancer agent in humans and animals, to its complex phylogeny, to the functions of viral proteins during the early and late phases of the productive cycle and during cell transformation, to the role of HPV in cancers other than ano-genital ones, to infection and cancer in animals, to the host immune response, and finally to the development of anti-viral vaccines, both extant and future.
Although the book has been conceived as an organic whole, each chapter contains enough information to stand alone on a particular topic. It is hoped that the readers, whether seasoned papillomavirologists, or new comers to the field, are inspired by the book to conquer ever new summits and explore ever new depths in the pursuit of the common goal to understand the virus and defeat it.
An authoritative reference on Human Papillomavirus (HPV) is provided by the new book Papillomavirus Research.
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