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SARS-CoV-2 Spike protein binds to bacterial lipopolysaccharide and boosts proinflammatory activity

Petruk, Ganna LU orcid ; 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 (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)
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author
; ; ; ; ; ; ; ; and
organization
publishing date
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}},
}