Peroxisomes are platforms for cytomegalovirus' evasion from the cellular immune response.
Peroxisomes are platforms for cytomegalovirus' evasion from the cellular immune response.
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DOI：
10.1038/srep26028
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发表时间：
2016-05-16
影响因子：
4.6
通讯作者：
Ribeiro D
中科院分区：
文献类型：
--
作者：
Magalhães AC;Ferreira AR;Gomes S;Vieira M;Gouveia A;Valença I;Islinger M;Nascimento R;Schrader M;Kagan JC;Ribeiro D
人类巨细胞病毒发展了独特的逃避涉及VMIA的细胞抗病毒反应的机制，VMIA是一种病毒编码的蛋白质，不仅能够防止细胞凋亡，而且还能抑制线粒体MAV下游的信号转导。VMIA已被证明定位于线粒体并触发其碎裂，这一现象被证明是信号抑制所必需的。在这里，我们证明了VMIA也定位于过氧化物体，诱导其碎裂，并抑制依赖于过氧化物体的抗病毒信号通路。重要的是，我们证明了过氧化体片段不是VMIA特异性抑制过氧化体MAV下游信号的必要条件。我们还发现VMIA与细胞质伴侣Pex19相互作用，这表明该病毒已经制定了一种策略来劫持过氧体膜蛋白的运输机制。此外，我们发现VMIA能够与过氧化体MAV特异地相互作用。我们的结果表明，过氧化体构成了逃避细胞抗病毒反应的平台，人类巨细胞病毒已经开发出一种机制，通过这种机制，它能够特异性地逃避依赖于过氧化物体MAVS的抗病毒信号。
The human cytomegalovirus developed distinct evasion mechanisms from the cellular antiviral response involving vMIA, a virally-encoded protein that is not only able to prevent cellular apoptosis but also to inhibit signalling downstream from mitochondrial MAVS. vMIA has been shown to localize at mitochondria and to trigger their fragmentation, a phenomenon proven to be essential for the signalling inhibition. Here, we demonstrate that vMIA is also localized at peroxisomes, induces their fragmentation and inhibits the peroxisomal-dependent antiviral signalling pathway. Importantly, we demonstrate that peroxisomal fragmentation is not essential for vMIA to specifically inhibit signalling downstream the peroxisomal MAVS. We also show that vMIA interacts with the cytoplasmic chaperone Pex19, suggesting that the virus has developed a strategy to highjack the peroxisomal membrane proteins’ transport machinery. Furthermore, we show that vMIA is able to specifically interact with the peroxisomal MAVS. Our results demonstrate that peroxisomes constitute a platform for evasion of the cellular antiviral response and that the human cytomegalovirus has developed a mechanism by which it is able to specifically evade the peroxisomal MAVS-dependent antiviral signalling.