Universität zu Köln

Moeckel, Maureen, Rahn, Elena, de la Cruz, Nydia, Wirtz, Lisa, van Lent, Jan W. M., Pijlman, Gorben P. and Knebel-Moersdorf, Dagmar (2019). Herpes Simplex Virus 1 Can Enter Dynamin 1 and 2 Double-Knockout Fibroblasts. J. Virol., 93 (16). WASHINGTON: AMER SOC MICROBIOLOGY. ISSN 1098-5514

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Abstract

Dynamin GTPases, best known for their role in membrane fission of endocytic vesicles, provide a target for viruses to be exploited during endocytic uptake. Recently, we found that entry of herpes simplex virus 1 (HSV-1) into skin cells depends on dynamin, although our results supported that viral internalization occurs via both direct fusion with the plasma membrane and via endocytic pathways. To further explore the role of dynamin for efficient HSV-1 entry, we utilized conditional dynamin 1 and dynamin 2 double-knockout (DKO) fibroblasts as an experimental tool. Strikingly, HSV-1 entered control and DKO fibroblasts with comparable efficiencies. For comparison, we infected DKO cells with Semliki Forest virus, which is known to adopt clathrin-mediated endocytosis as its internalization pathway, and observed efficient virus entry. These results support the notion that the DKO cells provide alternative pathways for viral uptake. Treatment of cells with the dynamin inhibitor dynasore confirmed that HSV-1 entry depended on dynamin in the control fibroblasts. As expected, dynasore did not interfere with viral entry into DKO cells. Electron microscopy of HSV-1-infected cells suggests viral entry after fusion with the plasma membrane and by endocytosis in both dynamin-expressing and dynamin-deficient cells. Infection at low temperatures where endocytosis is blocked still resulted in HSV-1 entry, although at a reduced level, which suggests that nonendocytic pathways contribute to successful entry. Overall, our results strengthen the impact of dynamin for HSV-1 entry, as only cells that adapt to the lack of dynamin allow dynamin-independent entry. IMPORTANCE The human pathogen herpes simplex virus 1 (HSV-1) can adapt to a variety of cellular pathways to enter cells. In general, HSV-1 is internalized by fusion of its envelope with the plasma membrane or by endocytic pathways, which reflects the high adaptation to differences in its target cells. The challenges are to distinguish whether multiple or only one of these internalization pathways leads to successful entry and, furthermore, to identify the mode of viral uptake. In this study, we focused on dynamin, which promotes endocytic vesicle fission, and explored how the presence and absence of dynamin can influence viral entry. Our results support the idea that HSV-1 entry into mouse embryonic fibroblasts depends on dynamin; however, depletion of dynamin still allows efficient viral entry, suggesting that alternative pathways present upon dynamin depletion can accomplish viral internalization.

Item Type:	Journal Article
Creators:	Creators Email ORCID ORCID Put Code Moeckel, Maureen UNSPECIFIED UNSPECIFIED UNSPECIFIED Rahn, Elena UNSPECIFIED UNSPECIFIED UNSPECIFIED de la Cruz, Nydia UNSPECIFIED UNSPECIFIED UNSPECIFIED Wirtz, Lisa UNSPECIFIED UNSPECIFIED UNSPECIFIED van Lent, Jan W. M. UNSPECIFIED UNSPECIFIED UNSPECIFIED Pijlman, Gorben P. UNSPECIFIED UNSPECIFIED UNSPECIFIED Knebel-Moersdorf, Dagmar UNSPECIFIED UNSPECIFIED UNSPECIFIED
URN:	urn:nbn:de:hbz:38-145612
DOI:	10.1128/JVI.00704-19
Journal or Publication Title:	J. Virol.
Volume:	93
Number:	16
Date:	2019
Publisher:	AMER SOC MICROBIOLOGY
Place of Publication:	WASHINGTON
ISSN:	1098-5514
Language:	English
Faculty:	Unspecified
Divisions:	Unspecified
Subjects:	no entry
Uncontrolled Keywords:	Keywords Language MEMBRANE FISSION; ENDOCYTIC ENTRY; LIPID RAFTS; CELLS; DYNASORE; PATHWAY; ACTIN; INTERNALIZATION; KERATINOCYTES; HERPESVIRUSES Multiple languages Virology Multiple languages
Refereed:	Yes
URI:	http://kups.ub.uni-koeln.de/id/eprint/14561