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Viral afterlife: SARS-CoV-2 as a reservoir of immunomimetic peptides that reassemble into proinflammatory supramolecular complexes, 2024, Zhang et al.

Discussion in 'Long Covid research' started by SNT Gatchaman, Feb 2, 2024.

  1. SNT Gatchaman

    SNT Gatchaman Senior Member (Voting Rights)

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    Viral afterlife: SARS-CoV-2 as a reservoir of immunomimetic peptides that reassemble into proinflammatory supramolecular complexes
    Zhang, Yue; Bharathi, Vanthana; Dokoshi, Tatsuya; de Anda, Jaime; Ursery, Lauryn Tumey; Kulkarni, Nikhil N.; Nakamura, Yoshiyuki; Chen, Jonathan; Luo, Elizabeth W. C.; Wang, Lamei; Xu, Hua; Coady, Alison; Zurich, Raymond; Lee, Michelle W.; Matsui, Tsutomu; Lee, HongKyu; Chan, Liana C.; Schepmoes, Athena A.; Lipton, Mary S.; Zhao, Rui; Adkins, Joshua N.; Clair, Geremy C.; Thurlow, Lance R.; Schisler, Jonathan C.; Wolfgang, Matthew C.; Hagan, Robert S.; Yeaman, Michael R.; Weiss, Thomas M.; Chen, Xinhua; Li, Melody M. H.; Nizet, Victor; Antoniak, Silvio; Mackman, Nigel; Gallo, Richard L.; Wong, Gerard C. L.

    It is unclear how severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection leads to the strong but ineffective inflammatory response that characterizes severe Coronavirus disease 2019 (COVID-19), with amplified immune activation in diverse cell types, including cells without angiotensin-converting enzyme 2 receptors necessary for infection. Proteolytic degradation of SARS-CoV-2 virions is a milestone in host viral clearance, but the impact of remnant viral peptide fragments from high viral loads is not known.

    Here, we examine the inflammatory capacity of fragmented viral components from the perspective of supramolecular self-organization in the infected host environment. Interestingly, a machine learning analysis to SARS-CoV-2 proteome reveals sequence motifs that mimic host antimicrobial peptides (xenoAMPs), especially highly cationic human cathelicidin LL-37 capable of augmenting inflammation. Such xenoAMPs are strongly enriched in SARS-CoV-2 relative to low-pathogenicity coronaviruses.

    Moreover, xenoAMPs from SARS-CoV-2 but not low-pathogenicity homologs assemble double-stranded RNA (dsRNA) into nanocrystalline complexes with lattice constants commensurate with the steric size of Toll-like receptor (TLR)-3 and therefore capable of multivalent binding. Such complexes amplify cytokine secretion in diverse uninfected cell types in culture (epithelial cells, endothelial cells, keratinocytes, monocytes, and macrophages), similar to cathelicidin’s role in rheumatoid arthritis and lupus.

    The induced transcriptome matches well with the global gene expression pattern in COVID-19, despite using <0.3% of the viral proteome. Delivery of these complexes to uninfected mice boosts plasma interleukin-6 and CXCL1 levels as observed in COVID-19 patients.

    Link | PDF (Proceedings of the National Academy of Sciences)
     
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  2. SNT Gatchaman

    SNT Gatchaman Senior Member (Voting Rights)

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  3. rvallee

    rvallee Senior Member (Voting Rights)

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    Getting a sense of cluster bombs here. Tiny code bombs executing pathogenic functions long after the mother bomb has fragmented. How weird to have insisted on "not a live virus" when viruses aren't even 'alive' and really just a bunch of proteins about which we still understand very little.

    The arrogance of forcing mass reinfections without knowing about all the possible effects is stunning. Especially as the message about not bothering with respiratory infections has been applied by millions to other viruses, such as measles. As was predictable.
     
  4. SNT Gatchaman

    SNT Gatchaman Senior Member (Voting Rights)

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  5. SNT Gatchaman

    SNT Gatchaman Senior Member (Voting Rights)

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    Selected quotes from introduction —

     
  6. SNT Gatchaman

    SNT Gatchaman Senior Member (Voting Rights)

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    Selected quotes from discussion —

     
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  7. SNT Gatchaman

    SNT Gatchaman Senior Member (Voting Rights)

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  8. Amw66

    Amw66 Senior Member (Voting Rights)

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    And other viruses ?
    May turn out to be very interesting.
     
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  9. Sasha

    Sasha Senior Member (Voting Rights)

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    Any big brains on the forum care to speculate on the implications for ME/CFS, given that Lipkin and others did what seemed at the time to be a fairly conclusive ruling-out of PwME having more of any viruses in their bodies than controls? Could we have this peptide problem instead? Or has this possibly already been ruled out by ME/CFS research (which I haven't been following closely lately)?

    @Simon M, @Jonathan Edwards ?
     
  10. Jonathan Edwards

    Jonathan Edwards Senior Member (Voting Rights)

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    I doubt it means very much even in the context of acute Covid, @Sasha.

    I cannot see any relevance to ME.
     
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  11. Simon M

    Simon M Senior Member (Voting Rights)

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    The studies were of viruses in either serum or plasma and didn't look at PBMCs (though you might expect infected PBMCs to shed viruses if the viruses were active) or other possible body reservoirs. Ideally, you would at least look for viruses in PBMCs.

    Sorry, no idea about peptides or the findings in LC of viral RNA and any relevance ot MEcfs
     
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  12. Ash

    Ash Senior Member (Voting Rights)

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    The consequences are so grave that as things stand I think the rich are going achieve their goal of annihilating most of humanity, as this pandemic rolls on merging with other pathogens old and new.
     

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