Interview: Functional Genomics of Papillomaviruses

New Virology Special Issue now available!

Human papillomavirus (HPV) has gained notoriety in the past few years with the introduction of HPV vaccines to prevent infection and subsequent development of cancer. HPV belongs to a bigger family of viruses – the papillomaviruses – which are explored by the collection of articles in a new Special Issue of Virology: Functional Genomics of Papillomaviruses.

Here we find out more from Paul F. Lambert, Howard M. Temin Professor of Oncology at the McArdle Laboratory for Cancer Research, University of Wisconsin, USA, who serves as an Editor for Virology and a Guest Editor for this Special Issue.

Papillomaviruses are an ancient group of viruses – what do we know about their evolutionary history?

Papillomaviruses infect a variety of mammals, birds and non-avian reptiles in a species specific manner, suggesting they have been around for a long time. The abundance of sequence data for this family of viruses (nearly 250 papillomaviruses have been isolated and sequenced) is now providing evolutionary biologists a wealth of data with which to assess what has driven the evolution of these viruses. In the Special Issue of Virology, there is an article dedicated to this new area of research. Several interesting concepts have emerged including the concept of ‘niche sorting’ in which the virus co-evolves with the host and the environment to infect specific ecological niches of the host. Another interesting concept is that the viral E6 and E7 oncoproteins, which are so important in driving human papillomavirus (HPV)-associated carcinogenesis, likely evolved from a common ancestor gene. The study of papillomavirus evolution is likely to guide future studies understanding the role of individual viral genes in the viral life cycle as well as their tumorigenic properties.

What sort of symptoms result from infection?

The most common symptom is the development of warts, which are benign lesions that are self-contained and usually regress over time. Certain HPVs are sexually transmitted (they are the most common sexually transmitted disease) and a subset of these (called the high risk HPVs) are associated with 5% of all human cancers including virtually all cervical cancers, most other anogenital cancers, and a growing fraction of head and neck cancers. The HPV vaccines hold great promise in reducing sexually transmitted papillomavirus infections and consequently cancers associated with these viruses.

What is the Papillomavirus Episteme (PAVE) bioinformatics website

This website is database on papillomaviruses that is an outgrowth of an earlier effort initiated back in the 1990s. That database provided transcription maps for multiple papillomaviruses and alignments of virally encoded proteins across all sequenced genomes. This was an important resource that helped in the discovery of many seminal features of this family of viruses including the ubiquitous presence of peptide motifs in the E7 proteins of many papillomaviruses that permit E7 to associate with the retinoblastoma tumor suppressor (and its relatives p107 and p130), the presence of specific peptide motifs in high risk human papillomavirus E6 proteins that permit these proteins to bind PDZ proteins, a property that has proven important in conferring tumorigenic/transforming activities to these E6 proteins, and the presence of specific peptide motifs in all viral E1 proteins that permit these proteins to function as ATP-dependent DNA helicases. The new website is a greatly expanded and updated resource that includes structural data on papillomaviral proteins, epigenetic as well as transcriptional data, viral genomic sequences, as well as updated alignment data for viral proteins. Since the 1980s, many more papillomaviruses have been sequenced from across many more host species making this resource of much greater value.

What is the aim of this Special Issue?

The aim of this Special Issue is to provide articles that discuss the data present in the database and summarize the knowledge gained from related studies in the field. As such this Special Issue provides the most complete and up to date compilation of knowledge in the papillomavirus field and should itself provide a wealth of knowledge to scientists both within and outside the papillomavirus field.

What is your particular area of research?

My lab studies the oncogenic human papillomaviruses that cause cancer. We have used in vivo models to define the individual roles of viral oncogenes (E5, E6, E7) in HPV-associated cancers including cervical, anal and head/neck cancers, determine their mechanisms of action, and define host/environmental co-factors that contribute to the cancers that arise as a consequence of high risk HPV infections. We also perform studies on the papillomaviral life cycle that is intricately tied to the differentiation program of the host epithelia they infect.

Read the Virology Special Issue for free on ScienceDirect.

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