HIV-1 DNA Flap formation promotes uncoating of the pre-integration complex at the nuclear pore

被引:219
作者
Arhel, Nathalie J.
Souquere-Besse, Sylvie
Munier, Sandie
Souque, Philippe
Guadagnini, Stéphanie
Rutherford, Sandra
Prévost, Marie-Christine
Allen, Terry D.
Chameau, Pierre
机构
[1] Inst Pasteur, Grp Virol Mol & Vectorol, Dept Virol, CNRS,URA 3015, F-75724 Paris 15, France
[2] CNRS, Inst Andre Lwoff, UPR 1983, Villejuif, France
[3] Inst Pasteur, Paris, France
[4] Christie Hosp, Paterson Inst Canc Res, CRC, Dept Cell & Struct Biol, Manchester, Lancs, England
关键词
central DNA flap; HIV-1; nuclear import; uncoating;
D O I
10.1038/sj.emboj.7601740
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
The HIV-1 central DNA Flap acts as a cis-acting determinant of HIV-1 genome nuclear import. Indeed, DNA-Flap re-insertion within lentiviral-derived gene transfer vectors strongly stimulates gene transfer efficiencies. In this study, we sought to understand the mechanisms by which the central DNA Flap mediates HIV-1 nuclear import. Here, we show that reverse transcription (RT degrees) occurs within an intact capsid (CA) shell, independently of the routing process towards the nuclear membrane, and that uncoating is not an immediate post-fusion event, but rather occurs at the nuclear pore upon RT degrees completion. We provide the first observation with ultrastructural resolution of intact intracellular HIV-1 CA shells by scanning electron microscopy. In the absence of central DNA Flap formation, uncoating is impaired and linear DNA remains trapped within an integral CA shell precluding translocation through the nuclear pore. These data show that DNA Flap formation, the very last event of HIV-1 RT degrees, acts as a viral promoting element for the uncoating of HIV-1 at the nuclear pore.
引用
收藏
页码:3025 / 3037
页数:13
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