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Antimicrobial Agents and Chemotherapy, December 2005, p. 4843-4852, Vol. 49, No. 12
0066-4804/05/$08.00+0     doi:10.1128/AAC.49.12.4843-4852.2005
Copyright © 2005, American Society for Microbiology. All Rights Reserved.

Activities of Acyclic Nucleoside Phosphonates against Orf Virus in Human and Ovine Cell Monolayers and Organotypic Ovine Raft Cultures

F. Dal Pozzo,1,4 G. Andrei,1 A. Holy,2 J. Van Den Oord,3 A. Scagliarini,4 E. De Clercq,1 and R. Snoeck4*

Rega Institute for Medical Research, K.U. Leuven, Belgium,1 Institute of Organic Chemistry and Biochemistry, Academy of Sciences of the Czech Republic, Praque, Czech Republic,2 Pathology Department, U.Z. Leuven, Belgium,3 Department of Veterinary Public Health and Animal Pathology, Alma Mater Studiorum, Bologna, Italy4

Received 8 February 2005/ Returned for modification 11 April 2005/ Accepted 26 August 2005

Orf virus, a member of the Parapoxvirus genus, causes a contagious pustular dermatitis in sheep, goats, and humans. Previous studies have demonstrated the activity of (S)-1-[3-hydroxy-2-(phosphonomethoxy)propyl]cytosine (HPMPC; cidofovir; Vistide) against orf virus in cell culture and humans. We have evaluated a broad range of acyclic nucleoside phosphonates (ANPs) against several orf virus strains in primary lamb keratinocytes (PLKs) and human embryonic lung (HEL) monolayers. HPMPC, (S)-9-[3-hydroxy-2-(phosphonomethoxy)propyl]-2,6- diaminopurine (HPMPDAP), and (R)-9-[3-hydroxy-2-(phosphonomethoxy)propoxy]-2,4-diaminopyrimidine (HPMPO-DAPy) were three of the most active compounds that were subsequently tested in a virus yield assay with PLK and HEL cells by virus titration and DNA quantification. HPMPC, HPMPDAP, and HPMPO-DAPy were evaluated for their activities against orf virus replication in organotypic epithelial raft cultures from differentiated PLK cells. At the highest concentrations (50 and 20 µg/ml), full protection was provided by the three drugs, while at 5 µg/ml, only HPMPDAP and HPMPC offered partial protection. The activities of the three compounds in the raft culture system were confirmed by quantification of infectious virus and viral DNA. These findings provide a rationale for the use of HPMPC and other ANPs in the treatment of orf (contagious ecthyma) in humans and animals.

* Corresponding author. Mailing address: Rega Institute for Medical Research, Katholieke Universtiteit Leuven, Minderbroedersstraat 10, B-3000 Leuven, Belgium. Phone: 32 16 337395. Fax: 32 16 337340. E-mail: Robert.Snoeck{at}rega.kuleuven.ac.be.

Antimicrobial Agents and Chemotherapy, December 2005, p. 4843-4852, Vol. 49, No. 12
0066-4804/05/$08.00+0     doi:10.1128/AAC.49.12.4843-4852.2005
Copyright © 2005, American Society for Microbiology. All Rights Reserved.



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