HIV-1 induces the formation of stable microtubules to enhance early infection.
HIV-1 induces the formation of stable microtubules to enhance early infection.
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DOI:
10.1016/j.chom.2013.10.012
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发表时间:
2013-11-13
影响因子:
30.3
通讯作者:
Naghavi MH
中科院分区:
文献类型:
--
作者:
Sabo Y;Walsh D;Barry DS;Tinaztepe S;de Los Santos K;Goff SP;Gundersen GG;Naghavi MH
Stable microtubule (MT) subsets form distinct networks from dynamic MTs and acquire distinguishing posttranslational modifications, notably detyrosination and acetylation. Acting as specialized tracks for vesicle and macromolecular transport, their formation is regulated by the end-binding protein, EB1, which recruits proteins that stabilize MTs. We show that HIV-1 induces the formation of acetylated and detyrosinated stable MTs early in infection. Although the MT depolymerizing agent nocodazole affected dynamic MTs, HIV-1 particles localized to nocodazole-resistant stable MTs and infection was minimally affected. EB1 depletion or expression of an EB1 carboxy-terminal fragment that acts as a dominant negative inhibitor of MT stabilization, prevented HIV-1-induced stable MT formation and suppressed early viral infection. Furthermore, we show that the HIV-1 matrix protein targets the EB1-binding protein, Kif4 to induce MT stabilization. Our findings illustrate how specialized MT-binding proteins mediate MT stabilization by HIV-1 and the importance of stable MT subsets in viral infection.
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