Universität zu Köln

Eisfeld, Hannah S., Simonis, Alexander ORCID: 0000-0003-2945-9897, Winter, Sandra, Chhen, Jason, Stroeh, Luisa J., Krey, Thomas, Koch, Manuel ORCID: 0000-0002-2962-7814, Theobald, Sebastian J. and Rybniker, Jan ORCID: 0000-0001-8351-2690 (2021). Viral Glycoproteins Induce NLRP3 Inflammasome Activation and Pyroptosis in Macrophages. Viruses-Basel, 13 (10). BASEL: MDPI. ISSN 1999-4915

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Abstract

Infections with viral pathogens are widespread and can cause a variety of different diseases. In-depth knowledge about viral triggers initiating an immune response is necessary to decipher viral pathogenesis. Inflammasomes, as part of the innate immune system, can be activated by viral pathogens. However, viral structural components responsible for inflammasome activation remain largely unknown. Here we analyzed glycoproteins derived from SARS-CoV-1/2, HCMV and HCV, required for viral entry and fusion, as potential triggers of NLRP3 inflammasome activation and pyroptosis in THP-1 macrophages. All tested glycoproteins were able to potently induce NLRP3 inflammasome activation, indicated by ASC-SPECK formation and secretion of cleaved IL-1 beta. Lytic cell death via gasdermin D (GSDMD), pore formation, and pyroptosis are required for IL-1 beta release. As a hallmark of pyroptosis, we were able to detect cleavage of GSDMD and, correspondingly, cell death in THP-1 macrophages. CRISPR-Cas9 knockout of NLRP3 and GSDMD in THP-1 macrophages confirmed and strongly support the evidence that viral glycoproteins can act as innate immunity triggers. With our study, we decipher key mechanisms of viral pathogenesis by showing that viral glycoproteins potently induce innate immune responses. These insights could be beneficial in vaccine development and provide new impulses for the investigation of vaccine-induced innate immunity.

Item Type:	Journal Article
Creators:	Creators Email ORCID ORCID Put Code Eisfeld, Hannah S. UNSPECIFIED UNSPECIFIED UNSPECIFIED Simonis, Alexander UNSPECIFIED orcid.org/0000-0003-2945-9897 UNSPECIFIED Winter, Sandra UNSPECIFIED UNSPECIFIED UNSPECIFIED Chhen, Jason UNSPECIFIED UNSPECIFIED UNSPECIFIED Stroeh, Luisa J. UNSPECIFIED UNSPECIFIED UNSPECIFIED Krey, Thomas UNSPECIFIED UNSPECIFIED UNSPECIFIED Koch, Manuel UNSPECIFIED orcid.org/0000-0002-2962-7814 UNSPECIFIED Theobald, Sebastian J. UNSPECIFIED UNSPECIFIED UNSPECIFIED Rybniker, Jan UNSPECIFIED orcid.org/0000-0001-8351-2690 UNSPECIFIED
URN:	urn:nbn:de:hbz:38-588090
DOI:	10.3390/v13102076
Journal or Publication Title:	Viruses-Basel
Volume:	13
Number:	10
Date:	2021
Publisher:	MDPI
Place of Publication:	BASEL
ISSN:	1999-4915
Language:	English
Faculty:	Unspecified
Divisions:	Unspecified
Subjects:	no entry
Uncontrolled Keywords:	Keywords Language MECHANISMS Multiple languages Virology Multiple languages
URI:	http://kups.ub.uni-koeln.de/id/eprint/58809