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Journal of Virology, February 2008, p. 1518-1525, Vol. 82, No. 3
0022-538X/08/$08.00+0     doi:10.1128/JVI.01704-07
Copyright © 2008, American Society for Microbiology. All Rights Reserved.

Induction of Paclitaxel Resistance by the Kaposi's Sarcoma-Associated Herpesvirus Latent Protein LANA2{triangledown}

C. Muñoz-Fontela,1,4,{dagger} L. Marcos-Villar,1,{dagger} F. Hernandez,2 P. Gallego,1,5 E. Rodriguez,1 J. Arroyo,1 S.-J. Gao,3 J. Avila,2 and C. Rivas1,5*

Departmento de Microbiologia II, Fac. Farmacia, Universidad Complutense de Madrid, Plaza Ramon y Cajal sn, Madrid 28040, Spain,1 Departmento de Biologia Molecular, Centro de Biologia Molecular Severo Ochoa, Universidad Autonoma Madrid, Madrid 28049, Spain,2 Department of Pediatrics and Children's Cancer Research Institute, The University of Texas Health Science Center at San Antonio, San Antonio, Texas 78229,3 Department of Oncological Sciences, Mount Sinai School of Medicine, One Gustave L. Levy Place, Box 1130, New York, New York 10029,4 Centro Nacional de Biotecnologia, CSIC, Darwin 3, Campus Universidad Autonoma Madrid, Madrid 28049, Spain5

Received 6 August 2007/ Accepted 12 November 2007

Kaposi's sarcoma-associated herpesvirus (KSHV) is the causal agent of both KS and primary effusion lymphoma (PEL). Although treatment with paclitaxel has significant antitumor activity in KS, drug resistance represents a major obstacle for improving the overall response and survival of PEL patients. The transcriptional pattern of KSHV is cell/tissue specific, as revealed by the fact that the viral latent protein LANA2 is detected exclusively in B cells. This paper focuses on the mechanism of paclitaxel resistance observed in PEL cells. Here we show that LANA2 protein modulates microtubule dynamics through its direct binding to polymerized microtubules, preventing microtubule stabilization induced by paclitaxel. This is the first demonstration of paclitaxel resistance induced by a viral protein and suggests a link between the expression of LANA2 and the resistance of PEL cells to paclitaxel.

* Corresponding author. Mailing address: Centro Nacional de Biotecnologia, CSIC, Darwin 3, Campus Universidad Autonoma, Madrid 28049, Spain. Phone: 34-91-5854837. Fax: 34-91-5854506. E-mail: crivas{at}cnb.uam.es

{triangledown} Published ahead of print on 21 November 2007.

{dagger} These authors contributed equally to this work.

Journal of Virology, February 2008, p. 1518-1525, Vol. 82, No. 3
0022-538X/08/$08.00+0     doi:10.1128/JVI.01704-07
Copyright © 2008, American Society for Microbiology. All Rights Reserved.





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