Accumulation of mutations in antibody and CD8 T cell epitopes in a B cell depleted lymphoma patient with chronic SARS-CoV-2 infection.

Autor:	Khatamzas E; Department of Medicine III, University Hospital, Ludwig-Maximilians University Munich, Munich, Germany. elham.khatamzas@med.uni-heidelberg.de.; Division of Infectious Diseases and Tropical Medicine, Center for Infectious Diseases, Heidelberg Hospital, Heidelberg, Germany. elham.khatamzas@med.uni-heidelberg.de.; COVID-19 Registry of the LMU Munich (CORKUM), University Hospital, Ludwig-Maximilians University Munich, Munich, Germany. elham.khatamzas@med.uni-heidelberg.de., Antwerpen MH; Bundeswehr, Institute of Microbiology Munich, Munich, Germany.; German Center for Infection Research (DZIF), partner site Munich, Munich, Germany., Rehn A; Bundeswehr, Institute of Microbiology Munich, Munich, Germany.; German Center for Infection Research (DZIF), partner site Munich, Munich, Germany., Graf A; Laboratory for Functional Genome Analysis, Gene Center, Ludwig-Maximilians University Munich, Munich, Germany., Hellmuth JC; Department of Medicine III, University Hospital, Ludwig-Maximilians University Munich, Munich, Germany.; COVID-19 Registry of the LMU Munich (CORKUM), University Hospital, Ludwig-Maximilians University Munich, Munich, Germany., Hollaus A; Department of Medicine III, University Hospital, Ludwig-Maximilians University Munich, Munich, Germany.; German Center for Infection Research (DZIF), partner site Munich, Munich, Germany., Mohr AW; Department of Medicine III, University Hospital, Ludwig-Maximilians University Munich, Munich, Germany.; German Center for Infection Research (DZIF), partner site Munich, Munich, Germany., Gaitzsch E; Department of Medicine III, University Hospital, Ludwig-Maximilians University Munich, Munich, Germany., Weiglein T; Department of Medicine III, University Hospital, Ludwig-Maximilians University Munich, Munich, Germany., Georgi E; Bundeswehr, Institute of Microbiology Munich, Munich, Germany.; German Center for Infection Research (DZIF), partner site Munich, Munich, Germany., Scherer C; COVID-19 Registry of the LMU Munich (CORKUM), University Hospital, Ludwig-Maximilians University Munich, Munich, Germany.; Department of Medicine I, University Hospital, Ludwig-Maximilians University Munich, Munich, Germany., Stecher SS; Department of Medicine II, University Hospital, Ludwig-Maximilians University Munich, Munich, Germany., Gruetzner S; Institute for Transfusion Medicine and Haemostasis, Medical Faculty, University of Augsburg, Augsburg, Germany., Blum H; Laboratory for Functional Genome Analysis, Gene Center, Ludwig-Maximilians University Munich, Munich, Germany., Krebs S; Laboratory for Functional Genome Analysis, Gene Center, Ludwig-Maximilians University Munich, Munich, Germany., Reischer A; Department of Medicine III, University Hospital, Ludwig-Maximilians University Munich, Munich, Germany., Leutbecher A; Department of Medicine III, University Hospital, Ludwig-Maximilians University Munich, Munich, Germany., Subklewe M; Department of Medicine III, University Hospital, Ludwig-Maximilians University Munich, Munich, Germany., Dick A; Laboratory for Immunogenetics, University of Munich, LMU, Munich, Germany., Zange S; Bundeswehr, Institute of Microbiology Munich, Munich, Germany.; German Center for Infection Research (DZIF), partner site Munich, Munich, Germany., Girl P; Bundeswehr, Institute of Microbiology Munich, Munich, Germany.; German Center for Infection Research (DZIF), partner site Munich, Munich, Germany., Müller K; Bundeswehr, Institute of Microbiology Munich, Munich, Germany.; German Center for Infection Research (DZIF), partner site Munich, Munich, Germany., Weigert O; Department of Medicine III, University Hospital, Ludwig-Maximilians University Munich, Munich, Germany.; German Cancer Consortium (DKTK), Munich, Germany., Hopfner KP; Gene Center and Department of Biochemistry, Ludwig-Maximilians-Universität München, Munich, Germany., Stemmler HJ; Department of Medicine III, University Hospital, Ludwig-Maximilians University Munich, Munich, Germany., von Bergwelt-Baildon M; Department of Medicine III, University Hospital, Ludwig-Maximilians University Munich, Munich, Germany.; COVID-19 Registry of the LMU Munich (CORKUM), University Hospital, Ludwig-Maximilians University Munich, Munich, Germany.; German Cancer Consortium (DKTK), Munich, Germany., Keppler OT; COVID-19 Registry of the LMU Munich (CORKUM), University Hospital, Ludwig-Maximilians University Munich, Munich, Germany.; German Center for Infection Research (DZIF), partner site Munich, Munich, Germany.; Max von Pettenkofer Institute & Gene Center, Virology, Faculty of Medicine, Ludwig-Maximilians University, Munich, Germany., Wölfel R; Bundeswehr, Institute of Microbiology Munich, Munich, Germany.; German Center for Infection Research (DZIF), partner site Munich, Munich, Germany., Muenchhoff M; COVID-19 Registry of the LMU Munich (CORKUM), University Hospital, Ludwig-Maximilians University Munich, Munich, Germany.; German Center for Infection Research (DZIF), partner site Munich, Munich, Germany.; Max von Pettenkofer Institute & Gene Center, Virology, Faculty of Medicine, Ludwig-Maximilians University, Munich, Germany., Moosmann A; Department of Medicine III, University Hospital, Ludwig-Maximilians University Munich, Munich, Germany.; German Center for Infection Research (DZIF), partner site Munich, Munich, Germany.
Jazyk:	angličtina
Zdroj:	Nature communications [Nat Commun] 2022 Sep 23; Vol. 13 (1), pp. 5586. Date of Electronic Publication: 2022 Sep 23.
DOI:	10.1038/s41467-022-32772-5
Abstrakt:	Antibodies against the spike protein of severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) can drive adaptive evolution in immunocompromised patients with chronic infection. Here we longitudinally analyze SARS-CoV-2 sequences in a B cell-depleted, lymphoma patient with chronic, ultimately fatal infection, and identify three mutations in the spike protein that dampen convalescent plasma-mediated neutralization of SARS-CoV-2. Additionally, four mutations emerge in non-spike regions encoding three CD8 T cell epitopes, including one nucleoprotein epitope affected by two mutations. Recognition of each mutant peptide by CD8 T cells from convalescent donors is reduced compared to its ancestral peptide, with additive effects resulting from double mutations. Querying public SARS-CoV-2 sequences shows that these mutations have independently emerged as homoplasies in circulating lineages. Our data thus suggest that potential impacts of CD8 T cells on SARS-CoV-2 mutations, at least in those with humoral immunodeficiency, warrant further investigation to inform on vaccine design. (© 2022. The Author(s).)
Databáze:	MEDLINE
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