Analysis of human immunodeficiency virus type 1 Gag dimerization-induced assembly

被引:41
作者
Alfadhli, A
Dhenub, TC
Still, A
Barklis, E
机构
[1] Oregon Hlth & Sci Univ, Vollum Inst, Portland, OR 97201 USA
[2] Oregon Hlth & Sci Univ, Dept Microbiol, Portland, OR 97201 USA
关键词
D O I
10.1128/JVI.79.23.14498-14506.2005
中图分类号
Q93 [微生物学];
学科分类号
071005 ; 100705 ;
摘要
The nucleocapsid (NC) domains of retrovirus precursor Gag (PrGag) proteins play an essential role in virus assembly. Evidence suggests that NC binding to viral RNA promotes dimerization of PrGag capsid (CA) domains, which triggers assembly of CA N-terminal domains (NTDs) into hexamer rings that are interconnected by CA C-terminal domains. To examine the influence of dimerization on human immunodeficiency virus type 1 (HIV-1) Gag protein assembly in vitro, we analyzed the assembly properties of Gag proteins in which NC domains were replaced with cysteine residues that could be linked via chemical treatment. In accordance with the model that Gag protein pairing triggers assembly, we found that cysteine cross-linking or oxidation reagents induced the assembly of virus-like particles. However, efficient assembly also was observed to be temperature dependent or required the tethering of NTDs. Our results suggest a multistep pathway for HIV-1 Gag protein assembly. In the first step, Gag protein pairing through NC-RNA interactions or C-terminal cysteine linkage fosters dimerization. Next, a conformational change converts assembly-restricted dimers or small oligomers into assembly-competent ones. At the final stage, final particle assembly occurs, possibly through a set of larger intermediates.
引用
收藏
页码:14498 / 14506
页数:9
相关论文
共 42 条
  • [1] Efficient particle production by minimal gag constructs which retain the carboxy-terminal domain of human immunodeficiency virus type 1 capsid-p2 and a late assembly domain
    Accola, MA
    Strack, B
    Göttlinger, HG
    [J]. JOURNAL OF VIROLOGY, 2000, 74 (12) : 5395 - 5402
  • [2] Hantavirus nucleocapsid protein coiled-coil domains
    Alfadhli, A
    Steel, E
    Finlay, L
    Bächinger, HP
    Barklis, E
    [J]. JOURNAL OF BIOLOGICAL CHEMISTRY, 2002, 277 (30) : 27103 - 27108
  • [3] Structural analysis of membrane-bound retrovirus capsid proteins
    Barklis, E
    McDermott, J
    Wilkens, S
    Schabtach, E
    Schmid, MF
    Fuller, S
    Karanjia, S
    Love, Z
    Jones, R
    Rui, YJ
    Zhao, XM
    Thompson, D
    [J]. EMBO JOURNAL, 1997, 16 (06) : 1199 - 1213
  • [4] BOISE L, 1999, J BIOL CHEM, V274, P27891
  • [5] Importance of basic residues in the nucleocapsid sequence for retrovirus Gag assembly and complementation rescue
    Bowzard, JB
    Bennett, RP
    Krisina, NK
    Ernst, SM
    Rein, A
    Wills, JW
    [J]. JOURNAL OF VIROLOGY, 1998, 72 (11) : 9034 - 9044
  • [6] Human immunodeficiency virus type 1 Gag polyprotein multimerization requires the nucleocapsid domain and RNA and is promoted by the capsid-dimer interface and the basic region of matrix protein
    Burniston, MT
    Cimarelli, A
    Colgan, J
    Curtis, SP
    Luban, J
    [J]. JOURNAL OF VIROLOGY, 1999, 73 (10) : 8527 - 8540
  • [7] In vitro assembly properties of human immunodeficiency virus type 1 Gag protein lacking the p6 domain
    Campbell, S
    Rein, A
    [J]. JOURNAL OF VIROLOGY, 1999, 73 (03) : 2270 - 2279
  • [8] SELF-ASSEMBLY IN-VITRO OF PURIFIED CA-NC PROTEINS FROM ROUS-SARCOMA VIRUS AND HUMAN-IMMUNODEFICIENCY-VIRUS TYPE-1
    CAMPBELL, S
    VOGT, VM
    [J]. JOURNAL OF VIROLOGY, 1995, 69 (10) : 6487 - 6497
  • [9] Modulation of HIV-like particle assembly in vitro by inositol phosphates
    Campbell, S
    Fisher, RJ
    Towler, EM
    Fox, S
    Issaq, HJ
    Wolfe, T
    Phillips, LR
    Rein, A
    [J]. PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 2001, 98 (19) : 10875 - 10879
  • [10] Basic residues in human immunodeficiency virus type 1 nucleocapsid promote virion assembly via interaction with RNA
    Cimarelli, A
    Sandin, S
    Höglund, S
    Luban, J
    [J]. JOURNAL OF VIROLOGY, 2000, 74 (07) : 3046 - 3057