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Journal of Virology, August 2006, p. 7769-7774, Vol. 80, No. 15
0022-538X/06/$08.00+0     doi:10.1128/JVI.02427-05
Copyright © 2006, American Society for Microbiology. All Rights Reserved.

Cyclosporine Increases Human Immunodeficiency Virus Type 1 Vector Transduction of Primary Mouse Cells

Josh A. Noser,1 Greg J. Towers,2 Ryuta Sakuma,1 Jean-Maurice Dumont,3 Mary K. L. Collins,4 and Yasuhiro Ikeda1,4*

Molecular Medicine Program, Mayo Clinic College of Medicine, Rochester, Minnesota,1 Department of Virology, University College London, London, United Kingdom,2 Debiopharm, 1000 Lausanne, Switzerland,3 Department of Immunology and Molecular Pathology, University College London, London, United Kingdom4

Received 17 November 2005/ Accepted 25 April 2006

Murine primary cells are poorly permissive to human immunodeficiency virus type 1 (HIV-1) vector infection. Retroviral infectivity is influenced by dominant inhibitors such as TRIM5{alpha}. Sensitivity to TRIM5{alpha} is altered by interactions between cyclophilin A and the HIV-1 capsid. Here we demonstrate that competitive inhibitors of cyclophilins, cyclosporine or the related Debio-025, stimulate HIV-1 vector transduction of primary murine cells, including bone marrow and macrophages, up to 20-fold. Unexpectedly, the infectivity of an HIV-1 mutant or a simian lentivirus that does not recruit cyclophilin A is also stimulated by these drugs. We propose that cyclosporine and related compounds will be useful tools for experimental infection of murine primary cells. It is possible that HIV-1 infection of murine cells is inhibited by dominant factors related to immunophilins.


* Corresponding author. Mailing address: Mayo Clinic College of Medicine, Molecular Medicine Program, Guggenheim 18-11c, 200 First St., SW, Rochester, MN 55905. Phone: (507) 538-0153. Fax: (507) 266-2122. E-mail: ikeda.yasuhiro{at}mayo.edu.


Journal of Virology, August 2006, p. 7769-7774, Vol. 80, No. 15
0022-538X/06/$08.00+0     doi:10.1128/JVI.02427-05
Copyright © 2006, American Society for Microbiology. All Rights Reserved.




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