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Journal of Virology, September 2007, p. 10195-10200, Vol. 81, No. 18
0022-538X/07/$08.00+0     doi:10.1128/JVI.01058-07
Copyright © 2007, American Society for Microbiology. All Rights Reserved.

Even Attenuated Bovine Leukemia Virus Proviruses Can Be Pathogenic in Sheep{triangledown}

Arnaud Florins,1 Nicolas Gillet,1 Mathieu Boxus,1 Pierre Kerkhofs,2 Richard Kettmann,1 and Luc Willems1*

Cellular and Molecular Biology, FNRS-FUSAGx, Gembloux, Belgium,1 Veterinary and Agrochemical Research Centre, Uccle, Belgium2

Received 16 May 2007/ Accepted 29 June 2007

Based on a reverse genetics approach, we previously reported that bovine leukemia virus (BLV) mutants harboring deletions in the accessory R3 and G4 genes persist at very low proviral loads and are unable to induce leukemia or lymphoma in sheep, indicating that these R3 and G4 gene sequences are required for pathogenesis. We now show that lymphoma can occur, albeit infrequently (1 case of 20) and after extended periods of latency (7 years). Direct sequencing and reinfection experiments demonstrated that lymphomagenesis was not due to the reversion of the mutant to the wild type. Similar observations with another type of attenuated mutant impaired in the transmembrane protein (TM) YXXL signaling motifs were made. We conclude that the R3 and G4 genes and the TM YXXL motifs are not strictly required for pathogenesis but that their integrity contributes to disease frequency and latency.

* Corresponding author. Mailing address: National Fund for Scientific Research, Molecular and Cellular Biology Laboratory, 13 avenue Maréchal Juin, 5030 Gembloux, Belgium. Phone: 32-(0)81-622157. Fax: 32-(0)81-613888. E-mail: willems.l{at}fsagx.ac.be

{triangledown} Published ahead of print on 11 July 2007.

Journal of Virology, September 2007, p. 10195-10200, Vol. 81, No. 18
0022-538X/07/$08.00+0     doi:10.1128/JVI.01058-07
Copyright © 2007, American Society for Microbiology. All Rights Reserved.



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