A LC3-interacting motif in the influenza A virus M2 protein is required to subvert autophagy and maintain virion stability.
A LC3-interacting motif in the influenza A virus M2 protein is required to subvert autophagy and maintain virion stability.
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DOI：
10.1016/j.chom.2014.01.006
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发表时间：
2014-02-12
影响因子：
30.3
通讯作者：
Randow F
中科院分区：
文献类型：
--
作者：
Beale R;Wise H;Stuart A;Ravenhill BJ;Digard P;Randow F
自噬循环利用细胞成分，保护细胞免受细胞内病原体的侵害。虽然病毒必须逃避自噬细胞的破坏，但有些病毒也可以为了自己的利益而破坏自噬。甲型流感病毒（IAV）逃避自噬的能力取决于基质2 （M2）离子通道蛋白。我们发现IAV M2的细胞质尾部直接与必需的自噬蛋白LC3相互作用，并促进LC3重新定位到意想不到的质膜目的地。LC3结合是由M2中高度保守的LC3相互作用区（LIR）介导的。在病毒感染的细胞中，LC3重新分配到质膜需要M2 LIR。M2中破坏LC3结合的突变会干扰丝状芽殖并降低病毒粒子的稳定性。因此，IAV通过模仿宿主短线性蛋白-蛋白相互作用基序来破坏自噬。这种策略可以通过增强病毒后代的稳定性来促进感染在生物体之间的传播。甲型流感挪用自噬通过M2的质子通道M2结合必要的自噬通过一个高度保守的蛋白LC3 LIR主题M2 LIR主题道德LC3的质膜突变LIR主题影响丝状病毒出芽和减少稳定比尔等人发现甲型流感病毒M2蛋白质包含一个细胞质LC3-interacting地区(LIR)主题,结合自噬蛋白LC3和转移到质膜病毒出芽。LIR基序破坏自噬，是促进丝状芽出和病毒体稳定性所必需的。
Autophagy recycles cellular components and defends cells against intracellular pathogens. While viruses must evade autophagocytic destruction, some viruses can also subvert autophagy for their own benefit. The ability of influenza A virus (IAV) to evade autophagy depends on the Matrix 2 (M2) ion-channel protein. We show that the cytoplasmic tail of IAV M2 interacts directly with the essential autophagy protein LC3 and promotes LC3 relocalization to the unexpected destination of the plasma membrane. LC3 binding is mediated by a highly conserved LC3-interacting region (LIR) in M2. The M2 LIR is required for LC3 redistribution to the plasma membrane in virus-infected cells. Mutations in M2 that abolish LC3 binding interfere with filamentous budding and reduce virion stability. IAV therefore subverts autophagy by mimicking a host short linear protein-protein interaction motif. This strategy may facilitate transmission of infection between organisms by enhancing the stability of viral progeny. Influenza A misappropriates autophagy via its M2 proton channel M2 binds the essential autophagy protein LC3 via a highly conserved LIR motif The M2 LIR motif relocalizes LC3 to the plasma membrane Mutations in the LIR motif affect filamentous budding and reduce stability of virus Beale et al. discover that the influenza A virus M2 protein contains a cytoplasmic LC3-interacting region (LIR) motif that binds to the autophagy protein LC3 and diverts it to the plasma membrane during virus budding. The LIR motif subverts autophagy and is required to promote filamentous budding and virion stability.
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影响因子：
64.8
作者：
Feng Z;Hensley L;McKnight KL;Hu F;Madden V;Ping L;Jeong SH;Walker C;Lanford RE;Lemon SM
通讯作者：
Lemon SM
影响因子：
16.8
作者：
Belshaw R;Gardner A;Rambaut A;Pybus OG
通讯作者：
Pybus OG
影响因子：
64.8
作者：
Ichimura, Y;Kirisako, T;Ohsumi, Y
通讯作者：
Ohsumi, Y
影响因子：
64.5
作者：
LAMB, RA;ZEBEDEE, SL;RICHARDSON, CD
通讯作者：
RICHARDSON, CD
影响因子：
30.3
作者：
Heaton NS;Randall G
通讯作者：
Randall G