Autophagic degradation of lamins facilitates the nuclear egress of herpes simplex virus type 1

Turan A, Grosche L, Krawczyk A, Mühl-Zürbes P, Drassner C, Düthorn A, Kummer M, Hasenberg M, Voortmann S, Jastrow H, Dörrie J, Schaft N, Kraner M, Doehner K, Sodeik B, Steinkasserer A, Heilingloh C (2019)

Publication Type: Journal article

Publication year: 2019

Journal

The Journal of Cell Biology Rockefeller University Press

Book Volume: 218

Pages Range: 508-523

Article Number: 508

Journal Issue: 2

DOI: 10.1083/jcb.201801151

Abstract

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.

Authors with CRIS profile

Alexandra Birzer Department of Immune Modulation Jan Dörrie Department of Dermatology Niels Schaft Department of Dermatology Max Kraner Lehrstuhl für Biochemie Alexander Steinkasserer Professur für Experimentelle Dermatologie Christiane Heilingloh Department of Immune Modulation

Involved external institutions

Universität Duisburg-Essen (UDE) DE Germany (DE) Universitätsklinikum Essen DE Germany (DE) Medizinische Hochschule Hannover (MHH) / Hannover Medical School DE Germany (DE)

How to cite

APA:

Turan, A., Grosche, L., Krawczyk, A., Mühl-Zürbes, P., Drassner, C., Düthorn, A.,... Heilingloh, C. (2019). Autophagic degradation of lamins facilitates the nuclear egress of herpes simplex virus type 1. The Journal of Cell Biology, 218(2), 508-523. https://doi.org/10.1083/jcb.201801151

MLA:

Turan, Aykut, et al. "Autophagic degradation of lamins facilitates the nuclear egress of herpes simplex virus type 1." The Journal of Cell Biology 218.2 (2019): 508-523.

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