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Journal of Virology, January 1999, p. 592-600, Vol. 73, No. 1
0022-538X/99/$04.00+0
Copyright © 1999, American Society for Microbiology. All rights reserved.

Interaction with the p6 Domain of the Gag Precursor Mediates Incorporation into Virions of Vpr and Vpx Proteins from Primate Lentiviruses

L. Selig,1 J.-C. Pages,2 V. Tanchou,3 S. Prévéral,1 C. Berlioz-Torrent,1 L. X. Liu,1 L. Erdtmann,1 J.-L. Darlix,3 R. Benarous,1 and S. Benichou1,*

INSERM CJF 97-03, Institut Cochin de Génétique Moléculaire, Université Paris V, 75014 Paris,1 Généthon, Evry,2 and INSERM U412, Ecole Normale Supérieure de Lyon, Lyon,3 France

Received 28 May 1998/Accepted 15 October 1998

Vpr and Vpx proteins from human and simian immunodeficiency viruses (HIV and SIV) are incorporated into virions in quantities equivalent to those of the viral Gag proteins. We demonstrate here that Vpr and Vpx proteins from distinct lineages of primate lentiviruses were able to bind to their respective Gag precursors. The capacity of HIV type 1 (HIV-1) Vpr mutants to bind to Pr55Gag was correlated with their incorporation into virions. Molecular analysis of these interactions revealed that they required the C-terminal p6 domain of the Gag precursors. While the signal for HIV-1 Vpr binding lies in the leucine triplet repeat region of the p6 domain reported to be essential for incorporation, SIVsm Gag lacking the equivalent region still bound to SIVsm Vpr and Vpx, indicating that the determinants for Gag binding are located upstream of this region of the p6 domain. Binding to Gag cleavage products showed that HIV-1 Vpr interacted directly with the nucleocapsid protein (NC), whereas SIVsm Vpr and Vpx did not interact with NC but with the p6 protein. These results (i) reveal differences between HIV-1 and SIVsm for the p6 determinants required for Vpr and Vpx binding to Gag and (ii) suggest that HIV-1 Vpr and SIVsm Vpr and Vpx interact with distinct cleavage products of the precursor following proteolytic processing in the virions.

* Corresponding author. Mailing address: INSERM CJF 97-03, ICGM, 24 Rue du Faubourg Saint-Jacques, 75014 Paris, France. Phone: (33) 1 44 41 25 67. Fax: (33) 1 44 41 23 99. E-mail: benichou{at}cochin.inserm.fr.

Journal of Virology, January 1999, p. 592-600, Vol. 73, No. 1
0022-538X/99/$04.00+0
Copyright © 1999, American Society for Microbiology. All rights reserved.


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