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

Autor:	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.
Jazyk:	angličtina
Zdroj:	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.
DOI:	10.1073/pnas.2300644120
Abstrakt:	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.
Databáze:	MEDLINE
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