Nuclear export of simian immunodeficiency virus Vpx protein

被引:12
作者
Singhal, Prabhat K. [1 ]
Kumar, P. Rajendra [1 ]
Rao, Malireddi R. K. Subba [1 ]
Mahalingam, Sundarasamy [1 ]
机构
[1] Mol Virol Lab, Ctr DNA Fingerprints & Diagnost, Hyderabad 500076, Andhra Pradesh, India
关键词
D O I
10.1128/JVI.00563-06
中图分类号
Q93 [微生物学];
学科分类号
071005 ; 100705 ;
摘要
Lentiviruses, human immunodeficiency viruses (HIVs), and simian immunodeficiency viruses (SIVs) are distinguished from oncoretroviruses by their ability to infect nondividing cells such as macrophages. Retroviruses must gain access to the host cell nucleus for replication and propagation. HIV and SIV preintegration complexes (PIC) enter nuclei after traversing the central aqueous channel of the limiting nuclear pore complex without membrane breakdown. Among the nucleophilic proteins, namely, matrix, integrase, Vpx, and Vpr, present in HIV type 2/SIV PIC, Vpx is implicated in nuclear targeting and is also available for incorporation into budding virions at the plasma membrane. The mechanisms of these two opposite functions are not known. We demonstrate that Vpx is a nucleocytoplasmic shuttling protein and contains two novel noncanonical nuclear import signals and a leptomycin B-sensitive nuclear export signal. In addition, Vpx interacts with the cellular tyrosine kinase Fyn through its C-terminal proline-rich motif Furthermore, our data indicate that Fyn kinase phosphorylates Vpx and regulates its export from nucleus. Replacement of conserved tryptophan residues within domain 41 to 63 and tyrosine residues at positions 66, 69, and 71 in Vpx impairs its nuclear export, virion incorporation, and SIV replication in macrophages. Nuclear export is essential to ensure the availability of Vpx in the cytoplasm for incorporation into virions, leading to efficient viral replication within nondividing cells.
引用
收藏
页码:12271 / 12282
页数:12
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共 54 条
  • [1] A conserved dileucine-containing motif in p6gag governs the particle association of Vpx and Vpr of simian immunodeficiency viruses SIVmac and SIVagm
    Accola, MA
    Bukovsky, AA
    Jones, MS
    Gottlinger, HG
    [J]. JOURNAL OF VIROLOGY, 1999, 73 (12) : 9992 - 9999
  • [2] Phosphorylation of Vpr regulates HIV type 1 nuclear import and macrophage infection
    Agostini, I
    Popov, S
    Hao, T
    Li, JH
    Dubrovsky, L
    Chaika, O
    Chaika, N
    Lewis, R
    Bukrinsky, M
    [J]. AIDS RESEARCH AND HUMAN RETROVIRUSES, 2002, 18 (04) : 283 - 288
  • [3] Crystal structure of the M1 protein-binding domain of the influenza A virus nuclear export protein (NEP/NS2)
    Akarsu, H
    Burmeister, WP
    Petosa, C
    Petit, I
    Müller, CW
    Ruigrok, RWH
    Baudin, F
    [J]. EMBO JOURNAL, 2003, 22 (18) : 4646 - 4655
  • [4] The specificity of the CRM1-Rev nuclear export signal interaction is mediated by RanGTP
    Askjaer, P
    Jensen, TH
    Nilsson, J
    Englmeier, L
    Kjems, J
    [J]. JOURNAL OF BIOLOGICAL CHEMISTRY, 1998, 273 (50) : 33414 - 33422
  • [5] Identification of the nuclear localization signal of human immunodeficiency virus type 2 Vpx
    Belshan, M
    Ratner, L
    [J]. VIROLOGY, 2003, 311 (01) : 7 - 15
  • [6] A NUCLEAR-LOCALIZATION SIGNAL WITHIN HIV-1 MATRIX PROTEIN THAT GOVERNS INFECTION OF NONDIVIDING CELLS
    BUKRINSKY, MI
    HAGGERTY, S
    DEMPSEY, MP
    SHAROVA, N
    ADZHUBEI, A
    SPITZ, L
    LEWIS, P
    GOLDFARB, D
    EMERMAN, M
    STEVENSON, M
    [J]. NATURE, 1993, 365 (6447) : 666 - 669
  • [7] Nucleocytoplasmic transport of macromolecules
    Corbett, AH
    Silver, PA
    [J]. MICROBIOLOGY AND MOLECULAR BIOLOGY REVIEWS, 1997, 61 (02) : 193 - +
  • [8] Dynamic disruptions in nuclear envelope architecture and integrity induced by HIV-1 Vpr
    de Noronha, CMC
    Sherman, MP
    Lin, HW
    Cavrois, MV
    Moir, RD
    Goldman, RD
    Greene, WC
    [J]. SCIENCE, 2001, 294 (5544) : 1105 - 1108
  • [9] NUCLEAR TARGETING SEQUENCES - A CONSENSUS
    DINGWALL, C
    LASKEY, RA
    [J]. TRENDS IN BIOCHEMICAL SCIENCES, 1991, 16 (12) : 478 - 481
  • [10] A novel nuclear export activity in HIV-1 matrix protein required for viral replication
    Dupont, S
    Sharova, N
    DéHoratius, C
    Virbasius, CMA
    Zhu, XC
    Bukrinskaya, AG
    Stevenson, M
    Green, MR
    [J]. NATURE, 1999, 402 (6762) : 681 - 685