A novel bovine papillomavirus (BPV-6) causing true epithelial papillomas of the mammary gland skin: A member of a proposed new BPV subgroup

Eight bovine papillomavirus (BPV) types, BPV-1-8, have been classified, based on genome nucleotide sequence similarities, in the genera Deltapapillomavirus (BPV-1 and -2), Epsilonpapillomavirus (BPV-5 and -8), Xipapillomavirus (BPV-3, -4 and -6) and an unassigned genus (BPV-7). We report here the complete genome sequence of two new BPV types isolated from separate epithelial squamous papilloma lesions on cattle teats. The genomes are 7303 and 7399 bp in length, respectively, and both have genetic organization and consensus motifs typical of papillomaviruses. A neighbour-joining phylogenetic tree revealed that both viruses cluster with BPV-3, -4 and -6. Nucleotide sequence identities of the BPV L1 major capsid protein of these two new BPVs with BPV-3, their closest relative, are 74.2 and 71.2 %, respectively. These results suggest that both viruses are new BPV types in the genus Xipapillomavirus, and they are designated BPV-9 and BPV-10.Bovine papillomavirus (BPV) is an aetiological agent associated with several forms of cutaneous and mucosal papillomas (Campo, 2002). Six different types of BPVs have been distinguished on the basis of DNA sequence relatedness. Each BPV is associated with type-specific lesions (Jarrett et al., 1984): BPV-1 and BPV-2 are classified in the genus Deltapapillomavirus and infect the epithelium and dermis, giving rise to fibropapillomas; BPV-3, BPV-4 and BPV-6 are classified in the genus Xipapillomavirus and are strictly epitheliotropic, inducing true epithelial papillomas, and BPV-5 is classified in the genus Epsilonpapillomavirus and infects the epithelium and dermis, inducing both fibropapillomas and true epithelial papillomas of the skin (Bloch et al., 1994;Campo 2002;de Villiers et al., 2004). Recently, 16 putative new BPV types were partially cloned and sequenced from healthy skin swabs (Antonsson & Hansson, 2002;Ogawa et al., 2004). Two of the BPVs were characterized further by cloning and sequencing their complete genomes. Phylogenetic analysis showed that both viruses were new BPV types: one was designated BPV-7 and classified as a member of a new papillomavirus (PV) genus, and the other was designated BPV-8 and classified as a member of the genus Epsilonpapillomavirus Tomita et al., 2007). However, the tumorigenic potential of these two new BPV types and the other 14 putative new BPV types has not been elucidated. In a previous report, we identified two putative new BPV types, designated BPV-Type I and BPV-Type II, which may have caused an outbreak of bovine teat papillomatosis in Japan (Maeda et al., 2007). BPV-Type I and II were identified by PCR amplification of a 590 bp DNA fragment within the BPV genome L1 major capsid protein gene (GenBank accession no. AB253592 for type I; no. AB253595 for type II). However, the remaining BPV-Type I and II genome sequences have not been reported. In this study, the complete genome sequences of BPV-Type I and II were determined. These sequencing and phylogenetic analysis results showed that BPV-Type I and II are new BPV types (designated...

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confidence: 99%

Genomic and phylogenetic analysis of two novel bovine papillomaviruses, BPV-9 and BPV-10

Hatama

Nobumoto

Kanno

2008

“…Moreover, BPV-4 is not related to BPV-1 or BPV-2 (Campo et al, 1980) which are most likely, and in those cases analysed in detail definitely are, the viruses responsible for tumour induction in heterologous hosts as previously reported (Lancaster et al, 1979;Moar et al, 1981 ;Pfister et al, 1981). In fact, BPV-4 is a member of a subgroup of BPVs unrelated to Short communication BPV-I/BPV-2 (Jarrett et al, 1984). In turn, the fact that BPV-4 can directly cause malignant tumours in a heterologous host is an important finding since it is BPV-4 which is associated with malignant cancer in the natural host (Jarrett et al, 1978b).…”

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confidence: 88%

“…Several bovine papillomaviruses (BPV) have been described (Campo et al, 1980Jarrett et al, 1984;Lancaster & Olson, 1978;Pfister et al, 1979). BPV type 4 (BPV-4) is particularly interesting since BPV-4-induced papillomas are found in cattle with squamous carcinoma of the alimentary tract which is associated with the eating of bracken fern (Pteridium aquilinum) (Campo et al, 1980;Jarrett et al, 1978a, b).…”

Section: Discussionmentioning

confidence: 99%

“…Unintegrated viral DNA and virM DNA isolated from virus particles from bovine alimentary tract papillomas revealed identical cleavage patterns with CpG methylation-resistant and -sensitive restriction enzymes: apparently there was no gross methylation of CpG sites in either case. The entire BPV-4 genome appeared to be represented in the tumour DNA.Several bovine papillomaviruses (BPV) have been described (Campo et al, 1980Jarrett et al, 1984;Lancaster & Olson, 1978;Pfister et al, 1979). BPV type 4 (BPV-4) is particularly interesting since BPV-4-induced papillomas are found in cattle with squamous carcinoma of the alimentary tract which is associated with the eating of bracken fern (Pteridium aquilinum) (Campo et al, 1980;Jarrett et al, 1978a, b).…”

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confidence: 99%

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Viral DNA Sequences Detected in a Hamster Liposarcoma Induced by Bovine Papillomavirus Type 4

Moar¹,

Jarrett²,

O’Neil³

1986

SUMMARYFollowing intradermal inoculation of bovine papillomavirus type 4 (BPV-4) into a Syrian hamster, a liposarcoma developed at the inoculation site 20 months later. The DNA of this tumour contained multiple copies of the BPV-4 genome which existed in a free unintegrated state. Unintegrated viral DNA and virM DNA isolated from virus particles from bovine alimentary tract papillomas revealed identical cleavage patterns with CpG methylation-resistant and -sensitive restriction enzymes: apparently there was no gross methylation of CpG sites in either case. The entire BPV-4 genome appeared to be represented in the tumour DNA.Several bovine papillomaviruses (BPV) have been described (Campo et al., 1980Jarrett et al., 1984;Lancaster & Olson, 1978;Pfister et al., 1979). BPV type 4 (BPV-4) is particularly interesting since BPV-4-induced papillomas are found in cattle with squamous carcinoma of the alimentary tract which is associated with the eating of bracken fern (Pteridium aquilinum) (Campo et al., 1980;Jarrett et al., 1978a, b). The BPV-4 genome is oncogenic since it transforms NIH 3T3 cells in culture and the resulting BPV-4 DNA-containing cell lines are tumourigenic in nude mice (Campo & Spandidos, 1983). So far, however, there are no reports of BPV-4 being directly carcinogenic in the natural or a heterologous host. Here we report, for the first time, the induction of a tumour in a Syrian hamster inoculated with BPV-4 and the analysis of the tumour DNA for BPV-4 DNA sequences.Six Syrian hamsters were injected with clarified 10% suspensions of BPV-containing bovine alimentary papillomas. One-hundred gl of this preparation, which had been checked for virus by electron microscopy and the viral DNA typed as BPV-4 by restriction cleavage, was inoculated both into the right buccal pouch and intradermally on the skin of the back. Twenty months later one of the hamsters developed a tumour at the inoculation site on the back. This soft tumour (2 × 1 cm) was histologically classified as a liposarcoma. There was no evidence of fibrocytic transformation and no secondary tumours were noted in the lungs, liver or kidneys.High molecular weight DNA was prepared using guanidinium thiocyanate extraction followed by CsC1 density centrifugation (Chirgwin et al., 1979). Approximately 20/.tg of DNA was obtained from the small amount of tissue available. To analyse the state and presence of any viral DNA in the liposarcoma DNA, Southern blots (Southern, 1975) of undigested and endonuclease-digested DNAs were prepared and hybridized to a variety of BPV DNAs. Of these DNAs, which included a number of recombinant molecules of pAT 153 containing inserts also of BPV-1 (pBV1), BPV-2 (pBV2), , only pBV4 hybridized to the tumour DNA. Undigested DNA revealed the presence of viral DNA forms I, II and III representing supercoiled (I) and relaxed (II) circular molecules, and linear molecules (III) (Fig. 1 a). The molecular weight of the form III molecule corresponded to 4.5 × 10 6, which is the molecular weight of linear BPV-4 DNA isolated from...

“…BPV-4 induces epithelial papillomas of the upper alimentary canal which become the focus for malignant transformation into squamous carcinomas in cattle feeding on bracken fern (Jarrett et al, 1978(Jarrett et al, , 1980. BPV-4 is one of the members of subgroup B of bovine papillomaviruses, which cause proliferation of epithelial cells only, have a small genome, and are evolutionarily distant from the viruses of subgroup A, all of which induce proliferation of both fibroblasts and keratinocytes (Jarrett et al, 1984). Subgroup A includes BPV-1, probably the best known of all papillomaviruses.…”

Section: Introductionmentioning

confidence: 99%

Transcriptional Organization of Bovine Papillomavirus Type 4

Smith

Patel

Campo

1986

SUMMARYSeven virus-specific RNA transcripts have been identified in tumours induced by bovine papillomavirus type 4 (BPV-4). The RNAs measured 4.2, 3.6, 3.0, 2.8, 1.9, 1.6 and 1.0 kilobases (kb). They were mapped on the viral genome by Northern blot hybridization to subgenomic probes, by cDNA hybridization to viral DNA fragments and by SI analysis of unlabelled and 3' and 5' end-labelled DNA fragments. All the RNA species are transcribed from the same DNA strand, are polyadenylated and with the exception of the 1.0 kb RNA internally spliced. The 3.0, 1.9, 1.6 and 1.0 kb RNAs share the same 3' polyadenylation site at nucleotide 4009 whereas the 4.2 kb RNA and the 2.8 kb RNA terminate near a polyadenylation site at nucleotide 7187. The 4.2 kb and the 2.8 kb RNAs are transcribed from the late open reading frames and encode the structural polypeptides; the 3.0, 1.9, 1.6 and 1.0 kb RNAs are transcribed from the early open reading frames and are the transcripts involved in viral replication and cellular transformation.