Bandicoot Blues
Today’s post is from regular guest blogger:
Ed Rybicki, Department of Molecular and Cell Biology, University of Cape Town, South Africa.
Now that the dust has begun to settle after the launch of Merck’s much-hyped Gardasil genital papillomavirus vaccine – discussed in MicrobiologyBytes here and here – people are turning again to looking at the natural history of the virus.
With some serious surprises…
There is a wonderfully-titled paper in the December issue of Journal of Virology describing a novel virus isolated from an Australian marsupial, which looks like a natural chimaera resulting from recombination between a cutaneous papillomavirus and a polyomavirus (A Novel Virus Detected in Papillomas and Carcinomas of the Endangered Western Barred Bandicoot (Perameles bougainville) Exhibits Genomic Features of both the Papillomaviridae and Polyomaviridae), from a collaborative group drawn from Murdoch University in Perth, WA, and the University of Leuven in Belgium.
They set out to look for papillomaviruses in lesions of a progressively debilitating cutaneous and mucocutaneous papillomatosis and carcinomatosis syndrome observed in captive and wild populations of the western barred bandicoot, using the relatively new technique of multiply-primed isothermal rolling-circle DNA amplification (RCA) – adapted from a natural phage replication process similar to that described here previously. 
It was a reasonable assumption that papillomaviruses were involved, given the type of lesions and the fact that papillomavirus sequences had previously been amplified out of other cutaneous lesions of marsupials – however, use of RCA would allow amplification of any circular DNA genome, given the non-specific nature of the technique which could show up “escapes” from even broad-spectrum degenerate primer PCR DNA amplifications. What they found was at first non-controversial: RCA products from lesions from several animals gave a ~7.5 kDa genomic DNA band after digestion with BamHI or SalI, typical of a papillomavirus; however, sequencing of the cloned DNA revealed that although the genomes did in fact contain the characteristic L1 and L2 structural protein ORFs of a papillomavirus, they also had the large-T and small-t antigen regulatory protein-coding ORFs typical of a polyomavirus – and on the opposite strand to the structural protein genes, also typical of polyomaviruses:
The natural assumption in this case would be that they had cloned an artifact of template-swapping in the RCA reaction: however, a number of checks using PCR with specific primers and sequencing of DNA from other animals confirmed the result. The newly-designated bandicoot papillomatosis carcinomatosis virus type 1 (BPCV1) DNA was subsequently found in 94.7% of fresh lesion tissue extracts, and 100% of bandicoots withe papillomatosis and carcinomatosis syndrome screened by skin swabbing, indicating it is almost certainly the causative agent.
This is a landmark finding in virology: the two families of viruses, while both classed as DNA tumour viruses, are very different indeed, and while it is possible they have a common origin, it is evolutionarily very distant indeed, given that the two groups have been cospeciating with their hosts over geological aeons. They both have circular dsDSNA genomes, and similar-looking particle morphology, but neither their structural nor their regulatory proteins have any discernible homology to one another – which means it is conceptually as likely to find a viable recombinant between them as it is to successfully cross a crocodile and a tortoise.
The authors explore a number of options in explaining just how such a tortodile or crocoise came to be, and appear to give equal credence to the possibilities of simple recombination between a papillomavirus and a polyomavirus, and that the virus is a descendant of the last common ancestor of the two groups of viruses. Their own analysis of phylogenetic relationships, however, places the putative L1 protein firmly among the beta- and gamma-papillomaviruses, which are viruses isolated from humans and associated with the condition of epidermodysplasia verruciformis in immunosuppressed people, and cutaneous lesions respectively. This indicates to me that an already-evolved cutaneous papillomavirus recombined with an as yet undiscovered representative of the family Polyomaviridae, to give a new and unexpectedly viable chimaeric offspring that has persisted in its unique biological niche.
What this result opens up is the possibility that there is a lot more of this going on than we knew about – and that techniques like RCA may be the key to unlocking a completely unsuspected world of virus diversity.
I have recently been participating in a to-and-fro evolutionary discussion in the columns of a local weekly newspaper, in the course of which one protagonist stoutly proclaimed that evolution was hokum because “like only begats like” [sic]. I would show him this virus as an example of what rubbish that statement is – if only he could understand it.
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Tags: Biology, Genetics, Guest, Microbiology, Science, Virology
