Vpx proteins of SIVmac239 and HIV-2ROD interact with the cytoskeletal protein alpha-actinin 1.
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, alpha-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 alpha-actinin 1. These findings suggest that the interaction with alpha-actinin 1 may play an important role in the transport of Vpx to the nucleus and in Vpx-mediated nuclear import of the PIC.
Mueller
Sandra M
SM
Institute of Clinical and Molecular Virology, University of Erlangen-Nuernberg, Schlossgarten 4, D-91054 Erlangen, Germany.
Jung
Ronny
R
Institute of Clinical and Molecular Virology, University of Erlangen-Nuernberg, Schlossgarten 4, D-91054 Erlangen, Germany.
Weiler
Sigrid
S
Institute of Clinical and Molecular Virology, University of Erlangen-Nuernberg, Schlossgarten 4, D-91054 Erlangen, Germany.
Lang
Sabine M
SM
Institute of Clinical and Molecular Virology, University of Erlangen-Nuernberg, Schlossgarten 4, D-91054 Erlangen, Germany.
D000185:Actinin / Q000378:metabolism*; D000595:Amino Acid Sequence; D000818:Animals; D001692:Biological Transport; D019556:COS Cells; D002522:Chlorocebus aethiops; D003593:Cytoplasm / Q000378:metabolism; D015498:HIV-2 / Q000737:chemistry / Q000378:metabolism*; D008969:Molecular Sequence Data; D011392:Proline; D017434:Protein Structure, Tertiary; D012191:Retroviridae Proteins / Q000378:metabolism*; D016415:Sequence Alignment; D015302:Simian Immunodeficiency Virus / Q000737:chemistry / Q000378:metabolism*; D014162:Transfection; D020798:Two-Hybrid System Techniques; D054334:Viral Regulatory and Accessory Proteins / Q000096:biosynthesis / Q000235:genetics / Q000378:metabolism*
D012191:Retroviridae Proteins; C074286:VPX protein, Human immunodeficiency virus 2; C513059:VPX protein, Simian immunodeficiency virus; D054334:Viral Regulatory and Accessory Proteins; D000185:Actinin; D011392:Proline