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Journal of Virology, November 2004, p. 12689-12693, Vol. 78, No. 22
0022-538X/04/$08.00+0     DOI: 10.1128/JVI.78.22.12689-12693.2004
Copyright © 2004, American Society for Microbiology. All Rights Reserved.

Vpr and Vpu Are Important for Efficient Human Immunodeficiency Virus Type 1 Replication and CD4+ T-Cell Depletion in Human Lymphoid Tissue Ex Vivo

Elke Rücker,1,2,{dagger} Jean-Charles Grivel,1,{dagger} Jan Münch,2 Frank Kirchhoff,2* and Leonid Margolis1*

Laboratory of Molecular and Cellular Biophysics, National Institute of Child Health and Human Development, Bethesda, Maryland,1 Department of Virology, University of Ulm, Ulm, Germany2

Received 18 March 2004/ Accepted 7 July 2004

The relevance of the accessory vpr, vpu, and nef genes for human immunodeficiency virus type 1 (HIV-1) replication in human lymphoid tissue (HLT), the major site of viral replication in vivo, is largely unknown. Here, we show that an individual deletion of nef, vpr, or vpu significantly decreases HIV-1 replication and prevents CD4+ T-cell depletion in ex vivo HLT. However, only combined defects in all three accessory genes entirely disrupt the replicative capacity of HIV-1. Our results demonstrate that nef, vpr, and vpu are all essential for efficient viral spread in HLT, suggesting an important role in AIDS pathogenesis.

* Corresponding author. Mailing address for Leonid Margolis: National Institute of Child Health, Building 10, Room 9D58, Bethesda, MD 20892. Phone: (301) 594-2476. Fax: (301) 480-0857. E-mail: margolis{at}helix.nih.gov. Mailing address for Frank Kirchhoff: Department of Virology, University of Ulm, Albert-Einstein-Allee 11, 89081 Ulm, Germany. Phone: 49-731-50023344. Fax: 49-731-50023337. E-mail: frank.kirchhoff{at}medizin.uni-ulm.de.

{dagger} E.R. and J.-C.G contributed equally to this work.

Journal of Virology, November 2004, p. 12689-12693, Vol. 78, No. 22
0022-538X/04/$08.00+0     DOI: 10.1128/JVI.78.22.12689-12693.2004
Copyright © 2004, American Society for Microbiology. All Rights Reserved.



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