SARS-CoV-2 Spike protein binds to bacterial lipopolysaccharide and boosts proinflammatory activity
(2020) In Journal of Molecular Cell Biology 12(12). p.916-932- Abstract
- There is a link between high lipopolysaccharide (LPS) levels in the blood and the metabolic syndrome, and metabolic syndrome predisposes patients to severe COVID-19. Here, we define an interaction between SARS-CoV-2 spike (S) protein and LPS, leading to aggravated inflammation in vitro and in vivo. Native gel electrophoresis demonstrated that SARS-CoV-2 S protein binds to LPS. Microscale thermophoresis yielded a KD of ∼47 nM for the interaction. Computational modeling and all-atom molecular dynamics simulations further substantiated the experimental results, identifying a main LPS-binding site in SARS-CoV-2 S protein. S protein, when combined with low levels of LPS, boosted nuclear factor-kappa B (NF-κB) activation in monocytic THP-1 cells... (More)
- There is a link between high lipopolysaccharide (LPS) levels in the blood and the metabolic syndrome, and metabolic syndrome predisposes patients to severe COVID-19. Here, we define an interaction between SARS-CoV-2 spike (S) protein and LPS, leading to aggravated inflammation in vitro and in vivo. Native gel electrophoresis demonstrated that SARS-CoV-2 S protein binds to LPS. Microscale thermophoresis yielded a KD of ∼47 nM for the interaction. Computational modeling and all-atom molecular dynamics simulations further substantiated the experimental results, identifying a main LPS-binding site in SARS-CoV-2 S protein. S protein, when combined with low levels of LPS, boosted nuclear factor-kappa B (NF-κB) activation in monocytic THP-1 cells and cytokine responses in human blood and peripheral blood mononuclear cells, respectively. The in vitro inflammatory response was further validated by employing NF-κB reporter mice and in vivo bioimaging. Dynamic light scattering, transmission electron microscopy, and LPS-FITC analyses demonstrated that S protein modulated the aggregation state of LPS, providing a molecular explanation for the observed boosting effect. Taken together, our results provide an interesting molecular link between excessive inflammation during infection with SARS-CoV-2 and comorbidities involving increased levels of bacterial endotoxins. (Less)
Please use this url to cite or link to this publication:
https://lup.lub.lu.se/record/a6eadacf-08a4-45dd-90f8-6ebd77510d91
- author
- Petruk, Ganna LU ; Puthia, Manoj LU ; Petrlova, Jitka LU ; Samsudin, Firdaus ; Strömdahl, Ann-Charlotte LU ; Cerps, Samuel LU ; Uller, Lena LU ; Kjellström, Sven LU ; Bond, Peter John and Schmidtchen, Artur LU
- organization
- publishing date
- 2020
- type
- Contribution to journal
- publication status
- published
- subject
- in
- Journal of Molecular Cell Biology
- volume
- 12
- issue
- 12
- pages
- 916 - 932
- publisher
- Oxford University Press
- external identifiers
-
- pmid:33295606
- scopus:85102909194
- ISSN
- 1759-4685
- DOI
- 10.1093/jmcb/mjaa067
- language
- English
- LU publication?
- yes
- id
- a6eadacf-08a4-45dd-90f8-6ebd77510d91
- date added to LUP
- 2021-01-02 22:54:28
- date last changed
- 2022-04-26 22:58:03
@article{a6eadacf-08a4-45dd-90f8-6ebd77510d91, abstract = {{There is a link between high lipopolysaccharide (LPS) levels in the blood and the metabolic syndrome, and metabolic syndrome predisposes patients to severe COVID-19. Here, we define an interaction between SARS-CoV-2 spike (S) protein and LPS, leading to aggravated inflammation in vitro and in vivo. Native gel electrophoresis demonstrated that SARS-CoV-2 S protein binds to LPS. Microscale thermophoresis yielded a KD of ∼47 nM for the interaction. Computational modeling and all-atom molecular dynamics simulations further substantiated the experimental results, identifying a main LPS-binding site in SARS-CoV-2 S protein. S protein, when combined with low levels of LPS, boosted nuclear factor-kappa B (NF-κB) activation in monocytic THP-1 cells and cytokine responses in human blood and peripheral blood mononuclear cells, respectively. The in vitro inflammatory response was further validated by employing NF-κB reporter mice and in vivo bioimaging. Dynamic light scattering, transmission electron microscopy, and LPS-FITC analyses demonstrated that S protein modulated the aggregation state of LPS, providing a molecular explanation for the observed boosting effect. Taken together, our results provide an interesting molecular link between excessive inflammation during infection with SARS-CoV-2 and comorbidities involving increased levels of bacterial endotoxins.}}, author = {{Petruk, Ganna and Puthia, Manoj and Petrlova, Jitka and Samsudin, Firdaus and Strömdahl, Ann-Charlotte and Cerps, Samuel and Uller, Lena and Kjellström, Sven and Bond, Peter John and Schmidtchen, Artur}}, issn = {{1759-4685}}, language = {{eng}}, number = {{12}}, pages = {{916--932}}, publisher = {{Oxford University Press}}, series = {{Journal of Molecular Cell Biology}}, title = {{SARS-CoV-2 Spike protein binds to bacterial lipopolysaccharide and boosts proinflammatory activity}}, url = {{http://dx.doi.org/10.1093/jmcb/mjaa067}}, doi = {{10.1093/jmcb/mjaa067}}, volume = {{12}}, year = {{2020}}, }