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| Status |
Public on Feb 21, 2022 |
| Title |
Activation of NLRP3 Inflammasome by Virus-like Particles of Human Polyomaviruses in Macrophages |
| Organism |
Homo sapiens |
| Experiment type |
Expression profiling by high throughput sequencing
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| Summary |
Viral antigens can activate phagocytes inducing inflammation but the mechanisms are barely explored. This study aimed to investigate the capability of viral oligomeric proteins of different structure to induce inflammatory response in macrophages. Human THP-1 cell line was used to prepare macrophages which were treated with filamentous nucleocapsid-like particles (NLPs) of paramyxoviruses and spherical virus-like particles (VLPs) of human polyomaviruses. The effects of viral proteins on cell viability, pro-inflammatory cytokines’ production and formation of NLRP3 inflammasome components, ASC specks, were investigated. Filamentous NLPs did not induce inflammation markers while spherical VLPs mediated inflammatory response followed by NLRP3 inflammasome activation. Inhibitors of cathepsins and K+ efflux decreased IL-1β levels and cell death indicating a complex inflammasome activation process. Similar activation pattern was observed in primary human macrophages treated with VLPs. Single cell RNAseq analysis of THP-1 cells revealed several cell activation states characterized by high expression of inflammation-related genes. This study provides new insights into interaction of viral proteins with innate immune cells and suggests that structural properties of oligomeric proteins may define cell activation pathways.
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| Overall design |
Single-cell RNA sequencing of in vitro differentiated macrophages treated with PBS (control, n=1), KI polyomavirus recombinant major capsid protein viral particles (KIPyV VLPs, n=1), or MC polyomavirus recombinant major capsid protein viral particles (MCPyV VLPs, n=1).
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| Contributor(s) |
Lučiūnaitė A, Dalgėdienė I, Žilionis R, Mašalaitė K, Norkienė M, Šinkūnas A, Gedvilaitė A, Kučinskaitė-Kodzė I, Žvirblienė A |
| Citation missing |
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| |
| Submission date |
Dec 10, 2021 |
| Last update date |
Feb 23, 2022 |
| Contact name |
Rapolas Zilionis |
| E-mail(s) |
rapolas.zilionis@bti.vu.lt
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| Organization name |
Vilnius University
|
| Department |
Life Sciences Center
|
| Lab |
Mazutis
|
| Street address |
Sauletekis av 7
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| City |
Vilnius |
| State/province |
LT |
| ZIP/Postal code |
10257 |
| Country |
Lithuania |
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| Platforms (1) |
| GPL18573 |
Illumina NextSeq 500 (Homo sapiens) |
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| Samples (7)
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| GSM5728579 |
KIPyV VLP-treated macrophages [kipyv_ix6] |
| GSM5728580 |
MCPyV VLP-treated macrophages [mcpyv_ix7] |
| GSM5728581 |
MCPyV VLP-treated macrophages [mcpyv_ix8] |
| GSM5728582 |
MCPyV VLP-treated macrophages [mcpyv_ix9] |
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| Relations |
| BioProject |
PRJNA787935 |
| SRA |
SRP350274 |
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