Autophagic degradation of lamins facilitates the nuclear egress of herpes simplex virus type 1
Autophagic degradation of lamins facilitates the nuclear egress of herpes simplex virus type 1
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DOI：
10.1083/jcb.201801151
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发表时间：
2018-12
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通讯作者：
Aykut Turan;Linda Grosche;A. Krawczyk;P. Mühl‐Zürbes;Christina Drassner;Alexandra Düthorn;M. Kummer;M. Hasenberg;Sylvia Voortmann;H. Jastrow;J. Dörrie;N. Schaft;M. Kraner;K. Döhner;B. Sodeik;A. Steinkasserer;C. S. Heilingloh
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作者：
Aykut Turan;Linda Grosche;A. Krawczyk;P. Mühl‐Zürbes;Christina Drassner;Alexandra Düthorn;M. Kummer;M. Hasenberg;Sylvia Voortmann;H. Jastrow;J. Dörrie;N. Schaft;M. Kraner;K. Döhner;B. Sodeik;A. Steinkasserer;C. S. Heilingloh
树突状细胞（dc）对诱导有效的抗病毒免疫反应至关重要。与未成熟的dc （idc）相比，成熟的dc （mdc）不允许感染1型单纯疱疹病毒（HSV-1）。在这里，我们证明了HSV-1感染肝癌细胞和肝癌细胞诱导自噬，这促进了肝癌细胞中层粘连蛋白A/C、B1和B2的降解。这反过来又促进了子代病毒衣壳的核出口，从而形成新的感染性颗粒。相比之下，由于低效率的自噬通量，在hsv -1感染的mdc中，层粘胶蛋白水平保持稳定。mDCs中KIF1B和KIF2A蛋白水平的升高可能通过阻碍自噬体-溶酶体融合来抑制层粘连蛋白降解。因此，在mDCs中，较少的子代衣壳从细胞核释放到细胞质中，较少的传染性病毒粒子被组装。我们假设，抑制mDCs中自噬层蛋白降解是一种非常强大的细胞反击，可以抑制子代病毒的产生，从而抑制病毒的传播。
Dendritic cells (DCs) are crucial for the induction of potent antiviral immune responses. In contrast to immature DCs (iDCs), mature DCs (mDCs) are not permissive for infection with herpes simplex virus type 1 (HSV-1). Here, we demonstrate that HSV-1 infection of iDCs and mDCs induces autophagy, which promotes the degradation of lamin A/C, B1, and B2 in iDCs only. This in turn facilitates the nuclear egress of progeny viral capsids and thus the formation of new infectious particles. In contrast, lamin protein levels remain stable in HSV-1–infected mDCs due to an inefficient autophagic flux. Elevated protein levels of KIF1B and KIF2A in mDCs inhibited lamin degradation, likely by hampering autophagosome–lysosome fusion. Therefore, in mDCs, fewer progeny capsids were released from the nuclei into the cytosol, and fewer infectious virions were assembled. We hypothesize that inhibition of autophagic lamin degradation in mDCs represents a very powerful cellular counterstrike to inhibit the production of progeny virus and thus viral spread.