PMID- 30587512 OWN - NLM STAT- MEDLINE DCOM- 20191210 LR - 20211204 IS - 1540-8140 (Electronic) IS - 0021-9525 (Print) IS - 0021-9525 (Linking) VI - 218 IP - 2 DP - 2019 Feb 4 TI - Autophagic degradation of lamins facilitates the nuclear egress of herpes simplex virus type 1. PG - 508-523 LID - 10.1083/jcb.201801151 [doi] AB - 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. CI - (c) 2019 Turan et al. FAU - Turan, Aykut AU - Turan A AUID- ORCID: 0000-0003-4259-8955 AD - Department of Immune Modulation, Universitatsklinikum Erlangen, Erlangen, Germany. FAU - Grosche, Linda AU - Grosche L AD - Department of Immune Modulation, Universitatsklinikum Erlangen, Erlangen, Germany. FAU - Krawczyk, Adalbert AU - Krawczyk A AUID- ORCID: 0000-0001-9502-9903 AD - Institute for Virology, University Hospital Essen, University of Duisburg-Essen, Essen, Germany. FAU - Muhl-Zurbes, Petra AU - Muhl-Zurbes P AD - Department of Immune Modulation, Universitatsklinikum Erlangen, Erlangen, Germany. FAU - Drassner, Christina AU - Drassner C AD - Department of Immune Modulation, Universitatsklinikum Erlangen, Erlangen, Germany. FAU - Duthorn, Alexandra AU - Duthorn A AD - Department of Immune Modulation, Universitatsklinikum Erlangen, Erlangen, Germany. FAU - Kummer, Mirko AU - Kummer M AD - Department of Immune Modulation, Universitatsklinikum Erlangen, Erlangen, Germany. FAU - Hasenberg, Mike AU - Hasenberg M AUID- ORCID: 0000-0001-7466-1846 AD - Imaging Center Essen, Electron Microscopy Unit, University Hospital of Essen, Essen, Germany. FAU - Voortmann, Sylvia AU - Voortmann S AD - Imaging Center Essen, Electron Microscopy Unit, University Hospital of Essen, Essen, Germany. FAU - Jastrow, Holger AU - Jastrow H AD - Imaging Center Essen, Electron Microscopy Unit, University Hospital of Essen, Essen, Germany. AD - Institute of Anatomy, University of Duisburg-Essen, Essen, Germany. FAU - Dorrie, Jan AU - Dorrie J AUID- ORCID: 0000-0002-3478-0741 AD - Department of Dermatology, Universitatsklinikum Erlangen, Erlangen, Germany. FAU - Schaft, Niels AU - Schaft N AUID- ORCID: 0000-0001-8236-9298 AD - Department of Dermatology, Universitatsklinikum Erlangen, Erlangen, Germany. FAU - Kraner, Max AU - Kraner M AUID- ORCID: 0000-0003-1733-1909 AD - Division of Biochemistry, Department of Biology, Friedrich-Alexander Universitat Erlangen-Nurnberg, Erlangen, Germany. FAU - Dohner, Katinka AU - Dohner K AUID- ORCID: 0000-0002-8222-3085 AD - Institute of Virology, Hannover Medical School, Hannover, Germany. FAU - Sodeik, Beate AU - Sodeik B AUID- ORCID: 0000-0003-4650-3036 AD - Institute of Virology, Hannover Medical School, Hannover, Germany. FAU - Steinkasserer, Alexander AU - Steinkasserer A AUID- ORCID: 0000-0001-7187-6729 AD - Department of Immune Modulation, Universitatsklinikum Erlangen, Erlangen, Germany alexander.steinkasserer@uk-erlangen.de. FAU - Heilingloh, Christiane Silke AU - Heilingloh CS AD - Department of Immune Modulation, Universitatsklinikum Erlangen, Erlangen, Germany christiane.heilingloh@gmx.de. LA - eng SI - RefSeq/NC_001806 PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20181226 PL - United States TA - J Cell Biol JT - The Journal of cell biology JID - 0375356 RN - 0 (KIF1B protein, human) RN - 0 (KIF2A protein, human) RN - 0 (Lamins) RN - EC 3.6.4.4 (Kinesins) SB - IM CIN - J Cell Biol. 2019 Feb 4;218(2):387-388. PMID: 30647098 MH - Capsid/*metabolism MH - *Cell Nucleus/metabolism/virology MH - *Cytosol/metabolism/virology MH - *Dendritic Cells/metabolism/virology MH - Herpesvirus 1, Human/genetics/*metabolism MH - Humans MH - Kinesins/genetics/metabolism MH - Lamins/genetics/metabolism MH - Proteolysis MH - Virus Release/*physiology PMC - PMC6363456 EDAT- 2018/12/28 06:00 MHDA- 2019/12/18 06:00 PMCR- 2019/08/04 CRDT- 2018/12/28 06:00 PHST- 2018/01/22 00:00 [received] PHST- 2018/10/02 00:00 [revised] PHST- 2018/11/08 00:00 [accepted] PHST- 2018/12/28 06:00 [pubmed] PHST- 2019/12/18 06:00 [medline] PHST- 2018/12/28 06:00 [entrez] PHST- 2019/08/04 00:00 [pmc-release] AID - jcb.201801151 [pii] AID - 201801151 [pii] AID - 10.1083/jcb.201801151 [doi] PST - ppublish SO - J Cell Biol. 2019 Feb 4;218(2):508-523. doi: 10.1083/jcb.201801151. Epub 2018 Dec 26.