Papillomaviruses: Evolution, Linnaean Taxonomy and Current Nomenclature

To the Editor

In a recent Opinion article by Bravo and colleagues published in Trends in Microbiology ¹, the authors argue for the clinical importance of understanding papillomavirus (PV) evolution. We are proponents of this approach to studying and interpreting data related to papillomaviruses as Dobzhansky stated, “nothing in biology makes sense except in the light of evolution” [2,3]. However, we disagree with some of the presented comments, particularly those relating to criticisms of the nomenclature system for papillomaviruses ^{2, 3}. We fail to see how the introduction of higher order taxa (supertaxa) would result in a better understanding of viral disease. We believe that papillomavirus systematics (the classification and nomenclature of papillomaviruses) and the use of an evolutionary approach to understand a specific phenotype (e.g., association with cancer) are two very different entities and serve complementary yet distinct purposes.

In the 2004 ³ and 2010 ⁴ versions of a proposed PV nomenclature, the L1 ORF was selected as the basis for viral classification. As was stated in both papers, this classification system was just that, and was not meant to represent a true history of extant papillomaviruses. It was created to serve the community in naming and classifying the multitude of characterized PVs. The 2010 paper incorporated the PV community’s and the International Committee on Taxonomy of Viruses (ICTV’s) views of viral classification. Papillomavirus biology, not just phylogeny, was an important consideration in these classification schemes.

Bravo and colleagues have been promoting the use of supertaxa in PV classification for several years. However, their classification scheme has not been embraced by the PV community (4 PV references in PubMed use the term, all by the Bravo-Gottschling group (accessed 08/30/2010)), and is poorly supported by biological/molecular or epidemiological data. The ICTV recognizes the term “ Subfamily” as a taxonomic level and states, “the taxon shall be used only when it is needed to solve a complex hierarchical problem” ⁵. Since the concept of supertaxa is neither required, nor simplifies PV nomenclature, no recommendation was made to incorporate this hierarchical level in papillomavirus taxonomy. Furthermore, introduction of terminology into the PV nomenclature lexicon without support of the PV community is divisive and does not facilitate communication between taxonomists, biologists, virologists, epidemiologists and clinicians who need to converse and exchange information about this medically important family of viruses. Furthermore, the Greek alphabet has and will continue to accommodate a growing number of PV genera. Also, it is well accepted by the field. A goal in establishing PV nomenclature is coherence and creation of a stable system. Classified PVs were historically named after the host from which the PV was isolated. This serves a useful function and has been only modified to keep the abbreviation of each PV unique. Lastly, the use and classification of microbes into genera serves an important function within and across research communities. No preconceived idea about the relationship between genera is supposed in PV nomenclature and it is not clear why Bravo et al., believe use of genera should inform degree of relationships between genera. As cited by the ICTV, “the primary purpose of naming a taxon is to supply a means of referring to the taxon”.

If, in contrast to reconstructing ancient phylogenetic relationships (e.g., use of Subfamilies) the goal is to integrate the evolved phenotypes (e.g., oncogenicity) of PVs, the theory of neutral evolution ⁶ predicts that most evolutionary changes will be background noise. It is likely that the study of closely related and recently evolved PVs with different phenotypes present a more tractable system ⁷. For example, the Alphapapillomavirus genus contains all human PVs for which sufficient evidence qualifies them as oncogenic for humans ⁸. The Alphapapillomavirus genus is a monophyletic clade and also contains viruses infecting non-human primates. However, the observation that viruses from several hosts cluster in a single clade does not make this clade paraphyletic, as suggested by Bravo et al. In fact, within this genus, the so-called high-risk viruses also form a monophyletic clade ⁹. If we apply, as suggested by Bravo et al. ¹, the supertaxon classification to this consideration, we have to include viruses infecting carnivores, swine and cetaceans for which (to date) no epidemiological evidence exists that they result in cancer. Not only does one need to take neutral evolution into account, but also selective pressure due to host-adaptation will undoubtedly have shaped the evolutionary history of these viruses in the distant past. Inclusion of these viruses would only serve to complicate the analysis. Whereas, we support Bravo and colleagues interest in spreading the importance of evolutionary biology in understanding PV oncogenesis, we do not believe that a mere reshuffling of taxonomic classification is of any help to the community. An increased effort in collecting epidemiogical data from animal viruses is of interest. A better understanding of diseases associated with animal PVs might allow us to detect subtleties not observed when only studying HPV phylo-epidemiology ⁹.