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Journal of Virology, September 2007, p. 9572-9576, Vol. 81, No. 17
0022-538X/07/$08.00+0     doi:10.1128/JVI.02803-06
Copyright © 2007, American Society for Microbiology. All Rights Reserved.

Proline 35 of Human Immunodeficiency Virus Type 1 (HIV-1) Vpr Regulates the Integrity of the N-Terminal Helix and the Incorporation of Vpr into Virus Particles and Supports the Replication of R5-Tropic HIV-1 in Human Lymphoid Tissue Ex Vivo{triangledown} ,{dagger}

Jörg Votteler,1 Nicole Studtrucker,1 Stefan Sörgel,1 Jan Münch,2 Elke Rücker,2 Frank Kirchhoff,2 Bernhard Schick,3 Peter Henklein,4 Torgils Fossen,5 Karsten Bruns,1,6 Alok Sharma,1,6 Victor Wray,6 and Ulrich Schubert1*

Institute of Virology, University of Erlangen-Nuremberg,1 Department of Otolaryngology, University Hospitals Erlangen-Nuremberg, Erlangen,3 Institute of Virology, University of Ulm, Ulm,2 Institute of Biochemistry, Humboldt University, Berlin,4 Department of Structural Biology, Helmholtz Centre for Infection Research, Braunschweig, Germany,6 Department of Chemistry, University of Bergen, Bergen, Norway5

Received 19 December 2006/ Accepted 30 May 2007

Mutational analysis of the four conserved proline residues in human immunodeficiency virus type 1 (HIV-1) Vpr reveals that only Pro-35 is required for efficient replication of R5-tropic, but not of X4-tropic, viruses in human lymphoid tissue (HLT) cultivated ex vivo. While Vpr-mediated apoptosis and G2 cell cycle arrest, as well as the expression and subcellular localization of Vpr, were independent, the capacity for encapsidation of Vpr into budding virions was dependent on Pro-35. 1H nuclear magnetic resonance data suggest that mutation of Pro-35 causes a conformational change in the hydrophobic core of the molecule, whose integrity is required for the encapsidation of Vpr, and thus, Pro-35 supports the replication of R5-tropic HIV-1 in HLT.

* Corresponding author. Mailing address: Schloßgarten 4, D-91054 Erlangen, Germany. Phone: 49-9131-85 26478. Fax: 49-9131-85 26182. E-mail: ulrich.schubert{at}viro.med.uni-erlangen.de

{triangledown} Published ahead of print on 6 June 2007.

{dagger} Supplemental material for this article may be found at http://jvi.asm.org/.

Journal of Virology, September 2007, p. 9572-9576, Vol. 81, No. 17
0022-538X/07/$08.00+0     doi:10.1128/JVI.02803-06
Copyright © 2007, American Society for Microbiology. All Rights Reserved.





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