In human astrocytes neurotropic flaviviruses increase autophagy, yet their replication is autophagy-independent.
In human astrocytes neurotropic flaviviruses increase autophagy, yet their replication is autophagy-independent.
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DOI：
10.1007/s00018-022-04578-7
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发表时间：
2022-10-25
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影响因子：
--
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星形胶质细胞是一种丰富的神经胶质细胞，是维持中枢神经系统内环境稳定的关键细胞。由于它们对感染的易感性，加上对病毒诱导的细胞死亡的高弹性，星形胶质细胞现在被认为是负责病毒在大脑内滞留和传播的主要细胞类型之一。自噬在清除细胞内成分和维持细胞内环境稳定方面起着重要作用，并且与病毒的生命周期密切相关。星形胶质细胞中自噬的生理意义，与病毒的生命周期和传播有关，仍然研究得很少。在本研究中，我们研究了黄病毒诱导的人类星形胶质细胞自噬的调制通过监测串联荧光标记的LC 3探针（mRFP-EGFP-LC 3）与共聚焦和超分辨率荧光显微镜。星形胶质细胞感染蜱传脑炎病毒（TBEV）或西尼罗河病毒（WNV），这两种致病性黄病毒，并与蚊子只有黄病毒（MOF），这被认为是非致病性。结果表明，人星形胶质细胞对TBEV、WNV感染敏感，对MOF的感染程度也低得多。TBEV和WNV的感染和复制率被增加的自噬率所抑制，而自噬体成熟和自噬区室的大小不受影响。雷帕霉素和渥曼青霉素对自噬的调节不影响TBEV和WNV的复制率，而巴弗洛霉素A1则减弱了它们的复制和感染性。在感染MOF的人星形胶质细胞中，这种黄病毒的低感染性和缺乏有效复制反映了缺乏自噬反应。在线版本包含补充材料，可通过10.1007/s 00018 -022-04578-7获得。
Astrocytes, an abundant type of glial cells, are the key cells providing homeostasis in the central nervous system. Due to their susceptibility to infection, combined with high resilience to virus-induced cell death, astrocytes are now considered one of the principal types of cells, responsible for virus retention and dissemination within the brain. Autophagy plays an important role in elimination of intracellular components and in maintaining cellular homeostasis and is also intertwined with the life cycle of viruses. The physiological significance of autophagy in astrocytes, in connection with the life cycle and transmission of viruses, remains poorly investigated. In the present study, we investigated flavivirus-induced modulation of autophagy in human astrocytes by monitoring a tandem fluorescent-tagged LC3 probe (mRFP-EGFP-LC3) with confocal and super-resolution fluorescence microscopy. Astrocytes were infected with tick-borne encephalitis virus (TBEV) or West Nile virus (WNV), both pathogenic flaviviruses, and with mosquito-only flavivirus (MOF), which is considered non-pathogenic. The results revealed that human astrocytes are susceptible to infection with TBEV, WNV and to a much lower extent also to MOF. Infection and replication rates of TBEV and WNV are paralleled by increased rate of autophagy, whereas autophagosome maturation and the size of autophagic compartments are not affected. Modulation of autophagy by rapamycin and wortmannin does not influence TBEV and WNV replication rate, whereas bafilomycin A1 attenuates their replication and infectivity. In human astrocytes infected with MOF, the low infectivity and the lack of efficient replication of this flavivirus are mirrored by the absence of an autophagic response. The online version contains supplementary material available at 10.1007/s00018-022-04578-7.
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影响因子：
3.7
作者：
Beatman E;Oyer R;Shives KD;Hedman K;Brault AC;Tyler KL;Beckham JD
通讯作者：
Beckham JD
影响因子：
7.8
作者：
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DOI：
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发表时间：
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期刊：
Nature reviews. Microbiology
影响因子：
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作者：
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通讯作者：
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影响因子：
3.2
作者：
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影响因子：
7.8
作者：
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