دورية أكاديمية
Viral afterlife: SARS-CoV-2 as a reservoir of immunomimetic peptides that reassemble into proinflammatory supramolecular complexes.
العنوان: | Viral afterlife: SARS-CoV-2 as a reservoir of immunomimetic peptides that reassemble into proinflammatory supramolecular complexes. |
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المؤلفون: | Zhang Y; Department of Bioengineering, University of California, Los Angeles, CA 90095.; Department of Chemistry and Biochemistry, University of California, Los Angeles, CA 9009.; California NanoSystems Institute, University of California, Los Angeles, CA 90095.; Department of Microbiology, Immunology & Molecular Genetics, University of California, Los Angeles, CA 90095.; Biomedical Engineering, School of Engineering, Westlake University, Hangzhou, Zhejiang 310012, China., Bharathi V; University of North Carolina Blood Research Center, Department of Medicine, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599., Dokoshi T; Department of Dermatology, University of California San Diego, La Jolla, CA 92093., de Anda J; Department of Bioengineering, University of California, Los Angeles, CA 90095.; Department of Chemistry and Biochemistry, University of California, Los Angeles, CA 9009.; California NanoSystems Institute, University of California, Los Angeles, CA 90095.; Department of Microbiology, Immunology & Molecular Genetics, University of California, Los Angeles, CA 90095., Ursery LT; University of North Carolina Blood Research Center, Department of Medicine, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599., Kulkarni NN; Department of Dermatology, University of California San Diego, La Jolla, CA 92093., Nakamura Y; Department of Dermatology, University of California San Diego, La Jolla, CA 92093., Chen J; Department of Bioengineering, University of California, Los Angeles, CA 90095.; Department of Chemistry and Biochemistry, University of California, Los Angeles, CA 9009.; California NanoSystems Institute, University of California, Los Angeles, CA 90095.; Department of Microbiology, Immunology & Molecular Genetics, University of California, Los Angeles, CA 90095., Luo EWC; Department of Bioengineering, University of California, Los Angeles, CA 90095.; Department of Chemistry and Biochemistry, University of California, Los Angeles, CA 9009.; California NanoSystems Institute, University of California, Los Angeles, CA 90095.; Department of Microbiology, Immunology & Molecular Genetics, University of California, Los Angeles, CA 90095., Wang L; Division of Gastroenterology, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA 02215., Xu H; Division of Gastroenterology, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA 02215., Coady A; Department of Pediatrics, School of Medicine, University of California San Diego, La Jolla, CA 92093., Zurich R; Department of Pediatrics, School of Medicine, University of California San Diego, La Jolla, CA 92093., Lee MW; Department of Bioengineering, University of California, Los Angeles, CA 90095.; Department of Chemistry and Biochemistry, University of California, Los Angeles, CA 9009.; California NanoSystems Institute, University of California, Los Angeles, CA 90095.; Department of Microbiology, Immunology & Molecular Genetics, University of California, Los Angeles, CA 90095., Matsui T; Stanford Synchrotron Radiation Lightsource, SLAC National Accelerator Laboratory, Stanford University, Menlo Park, CA 94025., Lee H; Division of Molecular Medicine, Harbor-University of California Los Angeles Medical Center, Los Angeles County, Torrance, CA 90502., Chan LC; Division of Molecular Medicine, Harbor-University of California Los Angeles Medical Center, Los Angeles County, Torrance, CA 90502.; Division of Infectious Diseases, Harbor-University of California Los Angeles Medical Center, Los Angeles County, Torrance, CA 90502.; Department of Medicine, David Geffen School of Medicine, University of California, Los Angeles, CA 90095.; Institute for Infection & Immunity, Lundquist Institute for Biomedical Innovation, Harbor-University of California Los Angeles Medical Center, Torrance, CA 90502., Schepmoes AA; Environmental Molecular Science Division, Pacific Northwest National Laboratory, Richland, WA 99354., Lipton MS; Environmental Molecular Science Division, Pacific Northwest National Laboratory, Richland, WA 99354., Zhao R; Environmental Molecular Science Division, Pacific Northwest National Laboratory, Richland, WA 99354., Adkins JN; Biological Science Division, Pacific Northwest National Laboratory, Richland, WA 99354., Clair GC; Biological Science Division, Pacific Northwest National Laboratory, Richland, WA 99354., Thurlow LR; Division of Oral and Craniofacial Health Sciences, Adams School of Dentistry, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599.; Department of Microbiology and Immunology, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599., Schisler JC; McAllister Heart Institute, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599.; Department of Pharmacology, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599.; Computational Medicine Program, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599., Wolfgang MC; Department of Microbiology and Immunology, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599.; Marsico Lung Institute, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599., Hagan RS; Marsico Lung Institute, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599.; Division of Pulmonary Diseases and Critical Care Medicine, Department of Medicine, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599., Yeaman MR; Division of Molecular Medicine, Harbor-University of California Los Angeles Medical Center, Los Angeles County, Torrance, CA 90502.; Division of Infectious Diseases, Harbor-University of California Los Angeles Medical Center, Los Angeles County, Torrance, CA 90502.; Department of Medicine, David Geffen School of Medicine, University of California, Los Angeles, CA 90095.; Institute for Infection & Immunity, Lundquist Institute for Biomedical Innovation, Harbor-University of California Los Angeles Medical Center, Torrance, CA 90502., Weiss TM; Stanford Synchrotron Radiation Lightsource, SLAC National Accelerator Laboratory, Stanford University, Menlo Park, CA 94025., Chen X; Division of Gastroenterology, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA 02215., Li MMH; Department of Microbiology, Immunology & Molecular Genetics, University of California, Los Angeles, CA 90095., Nizet V; Department of Pediatrics, School of Medicine, University of California San Diego, La Jolla, CA 92093., Antoniak S; Department of Pathology and Laboratory Medicine, University of North Carolina Blood Research Center, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599., Mackman N; University of North Carolina Blood Research Center, Department of Medicine, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599., Gallo RL; Department of Dermatology, University of California San Diego, La Jolla, CA 92093., Wong GCL; Department of Bioengineering, University of California, Los Angeles, CA 90095.; Department of Chemistry and Biochemistry, University of California, Los Angeles, CA 9009.; California NanoSystems Institute, University of California, Los Angeles, CA 90095.; Department of Microbiology, Immunology & Molecular Genetics, University of California, Los Angeles, CA 90095. |
المصدر: | Proceedings of the National Academy of Sciences of the United States of America [Proc Natl Acad Sci U S A] 2024 Feb 06; Vol. 121 (6), pp. e2300644120. Date of Electronic Publication: 2024 Feb 02. |
نوع المنشور: | Journal Article |
اللغة: | English |
بيانات الدورية: | Publisher: National Academy of Sciences Country of Publication: United States NLM ID: 7505876 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1091-6490 (Electronic) Linking ISSN: 00278424 NLM ISO Abbreviation: Proc Natl Acad Sci U S A Subsets: MEDLINE |
أسماء مطبوعة: | Original Publication: Washington, DC : National Academy of Sciences |
مواضيع طبية MeSH: | SARS-CoV-2* , COVID-19*, Humans ; Animals ; Mice ; Endothelial Cells ; Proteome ; Peptides |
مستخلص: | 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. Competing Interests: Competing interests statement:The authors declare no competing interest. |
References: | J Infect. 2020 Sep;81(3):e41-e43. (PMID: 32603675) FEBS Lett. 2008 May 28;582(12):1715-8. (PMID: 18448075) Proc Natl Acad Sci U S A. 2007 Oct 9;104(41):15994-9. (PMID: 17911256) Cells. 2021 Sep 26;10(10):. (PMID: 34685525) J Clin Med. 2020 Mar 31;9(4):. (PMID: 32244365) Am J Physiol Lung Cell Mol Physiol. 2019 Sep 1;317(3):L347-L360. (PMID: 31268347) JAMA. 2020 Apr 7;323(13):1239-1242. (PMID: 32091533) EBioMedicine. 2022 Jan;75:103812. (PMID: 35033854) Nat Immunol. 2021 Jul;22(7):829-838. (PMID: 33963333) Sci Rep. 2018 Mar 5;8(1):4032. (PMID: 29507358) Nature. 2007 Oct 4;449(7162):564-9. (PMID: 17873860) Crit Care Explor. 2020 Jun 22;2(6):e0144. (PMID: 32696007) Nat Rev Mol Cell Biol. 2022 Apr;23(4):286-301. (PMID: 34815573) Biochem Pharmacol. 2020 Dec;182:114225. (PMID: 32956643) Nucleic Acids Res. 2005 Jul 20;33(13):4053-64. (PMID: 16034027) J Immunol. 2018 Oct 15;201(8):2354-2368. (PMID: 30209189) Antimicrob Agents Chemother. 2012 Feb;56(2):658-65. (PMID: 22123683) Mol Cell. 2018 Oct 4;72(1):187-200.e6. (PMID: 30220560) Innovation (Camb). 2021 Jul 01;2(3):100141. (PMID: 34557778) Lancet Glob Health. 2017 Jan;5(1):e80-e88. (PMID: 27955791) Clin Dermatol. 2021 Mar-Apr;39(2):329-333. (PMID: 34272031) J Am Chem Soc. 2022 May 25;144(20):8945-8950. (PMID: 35579205) Nat Med. 2020 Jun;26(6):842-844. (PMID: 32398875) Annu Rev Phys Chem. 2010;61:171-89. (PMID: 20055668) ACS Nano. 2017 Dec 26;11(12):12145-12155. (PMID: 29016111) Nature. 2000 Dec 7;408(6813):740-5. (PMID: 11130078) J Exp Med. 2020 Dec 7;217(12):. (PMID: 32926097) Gastroenterology. 2020 Dec;159(6):2181-2192.e1. (PMID: 32841647) OMICS. 2012 May;16(5):284-7. (PMID: 22455463) Genome Biol. 2014;15(12):550. (PMID: 25516281) Nat Rev Microbiol. 2021 Mar;19(3):155-170. (PMID: 33116300) J Biol Chem. 2021 Jul;297(1):100828. (PMID: 34048712) Epidemiol Infect. 2016 Jun;144(8):1652-60. (PMID: 26808232) Nat Commun. 2021 May 11;12(1):2642. (PMID: 33976134) Proc Natl Acad Sci U S A. 2016 Nov 29;113(48):13588-13593. (PMID: 27849600) Emerg Microbes Infect. 2020 Dec;9(1):761-770. (PMID: 32228226) Nat Mater. 2015 Jul;14(7):696-700. (PMID: 26053762) Analyst. 2017 Jan 26;142(3):442-448. (PMID: 28091625) J Immunol. 2013 Nov 15;191(10):4895-901. (PMID: 24185823) Blood Adv. 2021 Mar 9;5(5):1164-1177. (PMID: 33635335) Nat Rev Microbiol. 2007 Sep;5(9):727-40. (PMID: 17703227) Clin Case Rep. 2020 Aug 30;8(12):2769-2772. (PMID: 33363819) Nat Immunol. 2020 Dec;21(12):1506-1516. (PMID: 33028979) Nature. 2022 Nov;611(7934):139-147. (PMID: 36044993) Lancet Rheumatol. 2020 Nov;2(11):e655-e657. (PMID: 33043303) Signal Transduct Target Ther. 2020 Jun 19;5(1):100. (PMID: 32561706) Nat Commun. 2019 Mar 4;10(1):1012. (PMID: 30833557) Sci Transl Med. 2011 Mar 9;3(73):73ra19. (PMID: 21389263) Dermatology. 2021;237(1):1-12. (PMID: 33232965) Genome Res. 2004 Oct;14(10B):2190-200. (PMID: 15489342) Eur J Pharmacol. 2002 Sep 6;451(1):1-10. (PMID: 12223222) Semin Cell Dev Biol. 2019 Apr;88:173-184. (PMID: 29432957) J Exp Med. 2021 Aug 2;218(8):. (PMID: 34128960) Proc Natl Acad Sci U S A. 2020 Jun 30;117(26):15193-15199. (PMID: 32522874) J Thromb Haemost. 2016 Jun;14(6):1238-48. (PMID: 26947929) Infect Immun. 2015 Nov 23;84(2):459-66. (PMID: 26597988) Nucleic Acids Res. 2021 Jan 8;49(D1):D545-D551. (PMID: 33125081) PLoS Comput Biol. 2017 Jan 5;13(1):e1005324. (PMID: 28056090) Science. 2013 Dec 6;342(6163):1188-93. (PMID: 24311680) Proc Natl Acad Sci U S A. 2021 Jun 22;118(25):. (PMID: 34083352) Proc Natl Acad Sci U S A. 2014 Dec 23;111(51):E5555-63. (PMID: 25489065) Elife. 2021 Oct 25;10:. (PMID: 34694226) Proc Natl Acad Sci U S A. 2021 Jan 5;118(1):. (PMID: 33372152) PLoS One. 2012;7(11):e50300. (PMID: 23209700) Shock. 2016 May;45(5):483-9. (PMID: 26717111) Nature. 2019 May;569(7755):236-240. (PMID: 31043745) Front Immunol. 2020 Jul 31;11:1629. (PMID: 32849553) Proc Natl Acad Sci U S A. 2011 Jul 5;108(27):10963-8. (PMID: 21690358) Nature. 2006 Jun 15;441(7095):840-6. (PMID: 16699522) Nature. 2002 Jan 24;415(6870):389-95. (PMID: 11807545) Nature. 2021 Jul;595(7865):107-113. (PMID: 33915569) Proc Natl Acad Sci U S A. 2004 May 11;101(19):7363-8. (PMID: 15118082) Nat Microbiol. 2022 Feb;7(2):262-276. (PMID: 35087228) Proc Natl Acad Sci U S A. 2019 Apr 2;116(14):6944-6953. (PMID: 30877253) Nat Med. 2020 Oct;26(10):1636-1643. (PMID: 32839624) EBioMedicine. 2021 Nov;73:103622. (PMID: 34678611) Nature. 2018 Nov;563(7730):197-202. (PMID: 30356220) |
معلومات مُعتمدة: | R37 AI052453 United States AI NIAID NIH HHS; S10 OD021512 United States OD NIH HHS; R01 HL142799 United States HL NHLBI NIH HHS; R35 HL155657 United States HL NHLBI NIH HHS; P30 GM133894 United States GM NIGMS NIH HHS; U54 CA260543 United States CA NCI NIH HHS; KL2 TR001882 United States TR NCATS NIH HHS; U01 AI124319 United States AI NIAID NIH HHS |
فهرسة مساهمة: | Keywords: antimicrobial peptides; inflammation; polyelectrolytes; self-assembly; superselectivity |
المشرفين على المادة: | 0 (Proteome) 0 (Peptides) |
تواريخ الأحداث: | Date Created: 20240202 Date Completed: 20240205 Latest Revision: 20240313 |
رمز التحديث: | 20240313 |
مُعرف محوري في PubMed: | PMC10861912 |
DOI: | 10.1073/pnas.2300644120 |
PMID: | 38306481 |
قاعدة البيانات: | MEDLINE |
تدمد: | 1091-6490 |
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DOI: | 10.1073/pnas.2300644120 |