Identification of a Novel Papillomavirus in a Northern Fulmar (Fulmarus glacialis) With Viral Production in Cartilage

Abstract

We report the identification of a novel papillomavirus, Fulmarus glacialis papillomavirus 1 (FgPV1), present within an interdigital foot mass of a Northern Fulmar (Fulmarus glacialis). The mass of interest was composed of normal stratified and keratinized epithelium and dense mesenchymal cells with central cartilaginous islands. Within the nuclei of many chondrocytes were loose aggregates or paracrystalline arrays of virions approximately 50 nm in size. Degenerate polymerase chain reaction was used to identify the virus as a putative papillomavirus, and the entire viral genome of 8132 base pairs was subsequently amplified and sequenced. Analysis revealed canonical papillomavirus architecture, including the early open reading frames E6, E7, E1, and E2 and the 2 late proteins L1 and L2. FgPV1 is most closely related to a cluster of avian and reptilian papillomaviruses as visualized by phylogenetic trees. This observation suggests that papillomavirus virion production can occur in mesenchymal cells. Keywords birds, histocytochemistry, chondrocytes, papillomavirus infections, inclusion bodies-viral, transmission electron microscopy, genome-viralThe Papillomaviridae family continues to expand with the ongoing discovery of previously unidentified species occupying over 30 different genera. 46 Avian papillomaviruses have been described in more than 12 avian species and 6 orders 27 since the 1970s. 28,33 In that time, only 3 have been fully sequenced: Francolinus leucoscepus papillomavirus 1 (FlPV1), Psittacus erithacus papillomavirus (PePV), and Fringilla coelebs papillomavirus (FcPV).31,41,44 Among species described so far, avian papillomaviruses and mammalian papillomaviruses share epitheliotropism and similar tissue distribution. In psittacines, virus has been detected in intestinal mucosal cells, 13,16,19,23,27,30,40 nasolacrimal epithelium, 13,16,22 and oral mucosa at the commissure of beaks. 22There is also a report of papillomavirus-associated growths on the legs and feet of two related finch species, Fringilla. coelebs and Fringilla montifringilla. 31 To date, there have been no reports of papillomaviruses or any neoplastic lesions in free-ranging seabirds despite the identification of papillomaviruses in numerous marine mammals, 5,35 including dolphins, 36,37 porpoises, 43 and sea turtles. 18Regardless of host species, productive papillomavirus infection (formation of infectious particles) has been invariably tied to the terminal differentiation of epithelial cells. A small number of papillomaviruses are capable of infecting and transforming fibroblasts, but these infections are considered nonproductive. The members of the Deltapapillomavirus genus such as bovine (Bos taurus) papillomaviruses 1 and 2 (BPV1, BPV2), for example, can infect fibroblasts in cattle, horses, and cats and is associated with transformation in these cells, causing the formation of fibropapillomas, also known as sarcoids in nonbovid species. 20 In these cases, virion production is considered limited to infected cells within the o...

Unique genome organization of non-mammalian papillomaviruses provides insights into the evolution of viral early proteins

“…Combining the inconclusive phylogenetic clustering with this additional molecular morphology data enables us to hypothesize that FgPV1 diverged from the other sauropsid papillomaviruses before the avian-turtle host animal diverged. This conclusion is further supported by the observation that FgPV1 lesions are uniquely associated with cartilage, while all other known papillomaviruses are primarily epithelial trophic ( Gaynor et al 2015 ).…”

“…However, the E6 proteins of all known sauropsid papillomaviruses contain only one such motif. Since the fish papillomavirus (SaPV1) does not contain any such motif ( Gaynor et al 2015 ), it is likely that the most recent common ancestor of the mammalian and sauropsid papillomaviruses had a single motif E6, which duplicated to give rise to the mammalian papillomavirus double Zinc finger motif in E6 ( Van Doorslaer et al 2009 ). The sauropsid (putative) E7 protein may be even more remarkable.…”

“…FgPV1 speciated before the split between the turtle and bird viruses. Of note, FgPV1 viral particles were found in the cartilaginous tissue of a Northern fulmar’s foot ( Gaynor et al 2015 ). Since papillomaviruses are typically associated with epithelial tissues, FgPV1 may be the prototype of a new group of papillomaviruses able to replicate within cartilage, a dramatically different host tissue.…”

“…To date, nine non-mammalian viruses have been described. These viruses infect birds including, yellow-necked francolin ( Francolinus leucoscepus ), common chaffinch ( Fringilla coelebs ), northern fulmar ( Fulmar glacialis ), African Grey parrot ( Psittacus erithacus ) and Adélie penguin ( Pygoscelis adeliae ) ( Terai et al 2002 ; Tachezy et al 2002 ; Van Doorslaer et al 2009 ; Varsani et al 2014 ; Gaynor et al 2015 ; Varsani et al 2015 ), as well as green sea turtle ( Chelonia mydas ), loggerhead sea turtle ( Caretta caretta ) ( Herbst et al 2009 ), Carpet python ( Morelia spilota ) ( Lange et al 2011 ), and gilt-head bream fish ( Sparus aurata ) ( Lopez-Bueno et al 2016 ).…”

Papillomaviruses: a systematic review

“…These data suggest that BPV-infected cell lines are a useful model to study the pathogenic mechanisms that lead to cancer. Our contribution has allowed to know the BPV prevalence and distribution in Brazil (Diniz et al , 2009; Carvalho et al , 2013; Lunardi et al , 2013; Melo et al , 2014; Araldi et al , 2014b; Cota et al , 2015; Gaynor et al , 2015a; Grindatto et al , 2015; Dong et al , 2016; Martano et al , 2016). These studies showed that the co-infection of at least two BPV types is frequent (Araldi et al , 2013, 2014a; Carvalho et al , 2013), demonstrating the importance to develop multivalent vaccines.…”