Vpx proteins of SIVmac239 and HIV-2ROD interact with the cytoskeletal protein {alpha}-actinin 1

• Published in: Journal of general virology Vol. 85; no. 11; p. 3291
• Main Authors: Mueller, Sandra M, Jung, Ronny, Weiler, Sigrid, Lang, Sabine M
• Format: Journal Article
• Language: English
• Published: Soc General Microbiol 01.11.2004
• ISSN: 0022-1317; 1465-2099
• DOI: 10.1099/vir.0.80198-0

Institute of Clinical and Molecular Virology, University of Erlangen-Nuernberg, Schlossgarten 4, D-91054 Erlangen, Germany Correspondence Sabine M. Lang sabine.lang{at}yale.edu vpx genes of human immunodeficiency virus type 2 (HIV-2) and immunodeficiency viruses from macaques (SIVmac), sooty mangabeys (SIVsm) and red-capped mangabeys (SIVrcm) encode a 112 aa protein that is packed into virion particles via interaction with the p6 domain of p55 gag . Vpx localizes to the nucleus when expressed in the absence of other viral proteins. Moreover, Vpx is necessary for efficient nuclear import of the pre-integration complex (PIC) and critical for virus replication in quiescent cells, such as terminally differentiated macrophages and memory T cells. Vpx does not contain sequence elements that are homologous to previously characterized nuclear localization signals (NLSs). Therefore, it is likely that Vpx-dependent import of the PIC is mediated by interaction of Vpx with cellular proteins that do not belong to the classical import pathways. By using a yeast two-hybrid screen, -actinin 1, a cytoskeletal protein, was identified to interact with SIVmac239 Vpx. Interestingly, deletion of the proline-rich C-terminal domain (aa 101–112) of Vpx, which is important for nuclear localization, resulted in loss of interaction with -actinin 1. These findings suggest that the interaction with -actinin 1 may play an important role in the transport of Vpx to the nucleus and in Vpx-mediated nuclear import of the PIC. Present address: Department of Pediatrics and Adolescent Medicine, University of Erlangen-Nuernberg, Loschgestr. 15, D-91054 Erlangen, Germany. Present address: Institute for Microbiology, Biochemistry and Genetics, Department of Biotechnology, Henkestrasse 91, D-91052 Erlangen, Germany. Present address: Yale University School of Medicine, Department of Pathology, PO Box 208023, 310 Cedar St, New Haven, CT 06520-8023, USA.