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Journal of Virology, December 2003, p. 13335-13347, Vol. 77, No. 24
0022-538X/03/$08.00+0     DOI: 10.1128/JVI.77.24.13335-13347.2003
Copyright © 2003, American Society for Microbiology. All Rights Reserved.

Complete Genomic Sequence and Comparative Analysis of the Tumorigenic Poxvirus Yaba Monkey Tumor Virus

Craig R. Brunetti,1,{dagger} Hiroko Amano,2 Yoshiaki Ueda,2 Jing Qin,1 Tatsuo Miyamura,2 Tetsuro Suzuki,2 Xing Li,3 John W. Barrett,1 and Grant McFadden1,4*

BioTherapeutics Research Group, Robarts Research Institute, London, Ontario, Canada N6G 2V4,1 Department of Microbiology and Immunology, University of Western Ontario, London, Ontario, Canada N6A 5C1,4 Laboratory of Tumor Viruses, National Institute of Infectious Diseases, Tokyo 162-8640, Japan,2 Viron Therapeutics Inc., London, Ontario, Canada N5G 2V43

Received 15 July 2003/ Accepted 4 September 2003

The Yatapoxvirus genus of poxviruses is comprised of Yaba monkey tumor virus (YMTV), Tanapox virus, and Yaba-like disease virus (YLDV), which all have the ability to infect primates, including humans. Unlike other poxviruses, YMTV induces formation of focalized histiocytomas upon infection. To gain a greater understanding of the Yatapoxvirus genus and the unique tumor formation properties of YMTV, we sequenced the 134,721-bp genome of YMTV. The genome of YMTV encodes at least 140 open reading frames, all of which are also found as orthologs in the closely related YLDV. However, 13 open reading frames found in YLDV are completely absent from YMTV. Common to both YLDV and YMTV are the unusually large noncoding regions between many open reading frames. To determine whether any of these noncoding regions might be functionally significant, we carried out a comparative analysis between the putative noncoding regions of YMTV and similar noncoding regions from other poxviruses. This approach identified three new gene poxvirus families, defined as orthologs of YMTV23.5L, YMTV28.5L, and YMTV120.5L, which are highly conserved in virtually all poxvirus species. Furthermore, the comparative analysis also revealed a 40-bp nucleotide sequence at approximately 14,700 bases from the left terminus that was 100% identical in the comparable intergene site within members of the Yatapoxvirus, Suipoxvirus, and Capripoxvirus genera and 95% conserved in the Leporipoxvirus genus. This conserved sequence was shown to function as a poxvirus late promoter element in transfected and infected cells, but other functions, such as an involvement in viral replication or packaging, cannot be excluded. Finally, we summarize the predicted immunomodulatory protein repertoire in the Yatapoxvirus genus as a whole.

* Corresponding author. Mailing address: BioTherapeutics Research Group, Robarts Research Institute, 1400 Western Rd., London, Ontario, Canada N6G 2V4. Phone: (519) 663-3184. Fax: (519) 663-3847. E-mail: mcfadden{at}robarts.ca.

{dagger} Present address: Department of Biology, Trent University, Peterborough, Ontario K9L 7B8, Canada.

Journal of Virology, December 2003, p. 13335-13347, Vol. 77, No. 24
0022-538X/03/$08.00+0     DOI: 10.1128/JVI.77.24.13335-13347.2003
Copyright © 2003, American Society for Microbiology. All Rights Reserved.



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