Department of Microbiology & Immunology1, and Departments of Pediatrics, Obstetrics & Gynecology and Womens Health, and Epidemiology & Social Medicine2, Comprehensive Cancer Center, Albert Einstein College of Medicine, 1300 Morris Park Avenue, Bronx, NY 10461, USA
Author for correspondence: Robert Burk. Fax +1 718 430 8975. e-mail burk{at}aecom.yu.edu
![]() |
Abstract |
---|
![]() ![]() ![]() ![]() |
---|
![]() |
Main text |
---|
![]() ![]() ![]() ![]() |
---|
To understand better the evolution and genetic determinants of PV pathogenicity, comparative molecular analysis of a wide variety of PV genomes is required. PVs have been detected in a variety of Felidae, including domestic cats (for review, see Sundberg et al., 2000 ). Domestic cats have been in close proximity to humans for centuries. Thus, they present an opportunity for horizontal transmission. To explore the origins and molecular characteristics of the cutaneous papillomavirus that infects domestic cats (Felis domesticus), we determined the complete nucleotide sequence of an isolate of F. domesticus papillomavirus (FdPV).
An FdPV genome isolated from a domestic cat with cutaneous papillomatosis was cloned in the EcoRI site of pUC18 (Carney et al., 1990 ; Sundberg et al., 2000
). The recombinant FdPV genome was amplified and purified (Qiagen Plasmid Mini Kit). To determine the nucleotide sequence, the cloned FdPV DNA was directly sequenced, initially with primers selected from the vector sequence and thereafter with additional primers designed by sequence walking. Sequencing was performed in the Einstein DNA sequencing core facility. The overlapping sequences were assembled manually and confirmed by sequencing the complementary strand. Several additional primers were designed and used to clarify sequence ambiguities. Once assembled, the sequence was analysed for homology with other PVs using BLAST software (Altschul et al., 1997
). The same software was used for protein sequence comparisons. Phylogenetic trees were created using PV sequences available from GenBank and The Human Papillomaviruses 1997 Compendium Online (http://hpv-web.lanl.gov/stdgen/virus/hpv/compendium/htdocs/HTML_FILES/HPVcompintro4.html#comp97). Phylogenetic trees were derived from individual open reading frames (ORFs) and non-coding regions (NCRs) to determine the relationship of FdPV to the available PV sequences using public domain software (Higgins & Sharp, 1988
).
A BLAST homology search using the nucleotide sequence of the FdPV L1 ORF revealed that it was most closely related to canine oral papillomavirus (COPV) (86% identity). The assembled sequence of the viral genome had a total size of 8300 bp with a G+C content of 46·12%. Examination of the FdPV sequence for potential genes showed a typical complement of PV ORFs, including overlaps between E1 and E2 and between L2 and L1, and the inclusion of an E4 ORF within E2. There was no initiation codon in the E4 ORF. The predicted ORFs are summarized in Table 1(a). The presence of an E5 ORF situated between the end of the E2 ORF and the start of the L2 ORF, which is found in some but not all PVs, was sought by comparison of all FdPV ORFs in this region to the complete PV database. None of the small FdPV ORFs in this region showed significant homology with known E5 ORFs. Table 1(b)
shows the degree of identity between putative FdPV proteins and the analogous proteins of the closest related PV, COPV. The identity of the amino acid sequence of the L1 ORF between FdPV and COPV was relatively higher (75·3%) than other ORFs, with identity to E1 (60·5%) and L2 (59·4%) also elevated compared with the E7 (53·1 %), E2 (50·5%) and E6 (40·4%) ORFs. This suggests that the E1, L1 and L2 ORFs are more conserved than the other ORFs, consistent with their essential role during PV evolution. To investigate the relationship of the FdPV genome with other PV sequences, the complete nucleotide sequence of FdPV was aligned with the corresponding sequences of other closely related PVs. The resulting phylogenetic tree was calculated based on available full-length sequences (de Villiers, 2001
). A representative tree is shown in Fig. 1
. FdPV was placed into the E3 group.
|
|
|
|
We have determined the complete nucleotide sequence of a PV isolated and cloned from a domestic cat with cutaneous papillomatous lesions. FdPV is most closely related to COPV by amino acid and nucleotide sequence homology and contains the novel NCR-2 region. PVs are considered highly species-specific and are not thought to cross the species barrier; however, there are exceptions in the veterinary literature (Perrott et al., 2000 ; Sundberg & O'Banion, 1989
). Nevertheless, a host switch or horizontal movement of virus from one species to another cannot be ruled out, although the divergence between these genomes indicates that they split long ago. In fact, 5366% of all codons had a third position change, suggesting that the genomes have been saturated by mutations. Subsequently each genome may have evolved as an independent entity by genetic drift. The lack of significant homology with human PVs indicates that recent horizontal transmission has not occurred. The cloning and characterization of FdPV has the potential to be utilized for development of an additional animal model of PV infection.
![]() |
Acknowledgments |
---|
![]() |
Footnotes |
---|
![]() |
References |
---|
![]() ![]() ![]() ![]() |
---|
Apt, D., Chong, T., Liu, Y. & Bernard, H. U. (1993). Nuclear factor I and epithelial cell-specific transcription of human papillomavirus type 16. Journal of Virology 67, 4455-4463.[Abstract]
Carney, H. C., England, J. J., Hodgin, E. C., Whiteley, H. E., Adkison, D. L. & Sundberg, J. P. (1990). Papillomavirus infection of aged Persian cats. Journal of Veterinary Diagnostic Investigation 2, 294-299.[Medline]
Chan, W. K., Chong, T., Bernard, H. U. & Klock, G. (1990). Transcription of the transforming genes of the oncogenic human papillomavirus-16 is stimulated by tumor promotors through AP1 binding sites. Nucleic Acids Research 18, 763-769.[Abstract]
Delius, H., Van Ranst, M. A., Jenson, A. B., zur Hausen, H. & Sundberg, J. P. (1994). Canine oral papillomavirus genomic sequence: a unique 1·5-kb intervening sequence between the E2 and L2 open reading frames. Virology 204, 447-452.[Medline]
de Villiers, E. M. (2001). Taxonomic classification of papillomaviruses. Papillomavirus Report 12, 57-63.
Dong, X. P., Stubenrauch, F., Beyer-Finkler, E. & Pfister, H. (1994). Prevalence of deletions of YY1-binding sites in episomal HPV 16 DNA from cervical cancers. International Journal of Cancer 58, 803-808.
Gloss, B. & Bernard, H. U. (1990). The E6/E7 promoter of human papillomavirus type 16 is activated in the absence of E2 proteins by a sequence-aberrant Sp1 distal element. Journal of Virology 64, 5577-5584.[Medline]
Higgins, D. G. & Sharp, P. M. (1988). CLUSTAL: a package for performing multiple sequence alignment on a microcomputer. Gene 73, 237-244.[Medline]
Ishiji, T., Lace, M. J., Parkkinen, S., Anderson, R. D., Haugen, T. H., Cripe, T. P., Xiao, J. H., Davidson, I., Chambon, P. & Turek, L. P. (1992). Transcriptional enhancer factor (TEF)-1 and its cell-specific co-activator activate human papillomavirus-16 E6 and E7 oncogene transcription in keratinocytes and cervical carcinoma cells. EMBO Journal 11, 2271-2281.[Abstract]
Lu, J. Z., Sun, Y. N., Rose, R. C., Bonnez, W. & McCance, D. J. (1993). Two E2 binding sites (E2BS) alone or one E2BS plus an A/T-rich region are minimal requirements for the replication of the human papillomavirus type 11 origin. Journal of Virology 67, 7131-7139.[Abstract]
May, M., Dong, X. P., Beyer-Finkler, E., Stubenrauch, F., Fuchs, P. G. & Pfister, H. (1994). The E6/E7 promoter of extrachromosomal HPV16 DNA in cervical cancers escapes from cellular repression by mutation of target sequences for YY1. EMBO Journal 13, 1460-1466.[Abstract]
Novacek, M. J. (2001). Mammalian phylogeny: genes and supertrees. Current Biology 11, R573-R575.[Medline]
Perrott, M. R., Meers, J., Greening, G. E., Farmer, S. E., Lugton, I. W. & Wilks, C. R. (2000). A new papillomavirus of possums (Trichosurus vulpecula) associated with typical wart-like papillomas. Archives of Virology 145, 1247-1255.[Medline]
Peterson, M. G., Tanese, N., Pugh, B. F. & Tjian, R. (1990). Functional domains and upstream activation properties of cloned human TATA binding protein. Science 248, 1625-1630.[Medline]
Sun, Y. N., Lu, J. Z. & McCance, D. J. (1996). Mapping of HPV-11 E1 binding site and determination of other important cis elements for replication of the origin. Virology 216, 219-222.[Medline]
Sundberg, J. P. & O'Banion, M. K. (1989). Animal papillomaviruses associated with malignant tumors. Advances in Viral Oncology 8, 55-71.
Sundberg, J. P., Smith, E. K., Herron, A. J., Jenson, A. B., Burk, R. D. & Van Ranst, M. (1994). Involvement of canine oral papillomavirus in generalized oral and cutaneous verrucosis in a Chinese Shar Pei dog. Veterinary Pathology 31, 183-187.[Abstract]
Sundberg, J. P., Van Ranst, M., Burk, R. D. & Jenson, A. B. (1996). The nonhuman (animal) papillomaviruses: host range, epitope conservation, and molecular diversity. In Human Papillomavirus Infections in Dermatology and Venereology , pp. 47-68. Edited by G. von Krogh & G. Gross. Boca Raton, FL: CRC Press.
Sundberg, J. P., Van Ranst, M., Montali, R., Homer, B. L., Miller, W. H., Rowland, P. H., Scott, D. W., England, J. J., Dunstan, R. W., Mikaelian, I. & Jenson, A. B. (2000). Feline papillomas and papillomaviruses. Veterinary Pathology 37, 1-10.
Received 15 February 2002;
accepted 19 April 2002.
HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
INT J SYST EVOL MICROBIOL | MICROBIOLOGY | J GEN VIROL |
J MED MICROBIOL | ALL SGM JOURNALS |