The anti-SARS-CoV-2 BNT162b2 vaccine suppresses mithramycin-induced erythroid differentiation and expression of embryo-fetal globin genes in human erythroleukemia K562 cells
The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is causative of the ongoing coronavirus disease 2019 (COVID-19) pandemic. The SARS-CoV-2 Spike protein (S-protein) plays an important role in the early phase of SARS-CoV-2 infection through efficient interaction with ACE2. The S-protei...
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| Veröffentlicht in: | Experimental cell research 2023-12, Vol.433 (2), p.113853-113853, Article 113853 |
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| creator | Zurlo, Matteo Gasparello, Jessica Verona, Marco Papi, Chiara Cosenza, Lucia Carmela Finotti, Alessia Marzaro, Giovanni Gambari, Roberto |
| description | The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is causative of the ongoing coronavirus disease 2019 (COVID-19) pandemic. The SARS-CoV-2 Spike protein (S-protein) plays an important role in the early phase of SARS-CoV-2 infection through efficient interaction with ACE2. The S-protein is produced by RNA-based COVID-19 vaccines, that were fundamental for the reduction of the viral spread within the population and the clinical severity of COVID-19. However, the S-protein has been hypothesized to be responsible for damaging cells of several tissues and for some important side effects of RNA-based COVID-19 vaccines. Considering the impact of COVID-19 and SARS-CoV-2 infection on the hematopoietic system, the aim of this study was to verify the effect of the BNT162b2 vaccine on erythroid differentiation of the human K562 cell line, that has been in the past intensively studied as a model system mimicking some steps of erythropoiesis. In this context, we focused on hemoglobin production and induced expression of embryo-fetal globin genes, that are among the most important features of K562 erythroid differentiation. We found that the BNT162b2 vaccine suppresses mithramycin-induced erythroid differentiation of K562 cells. Reverse-transcription-qPCR and Western blotting assays demonstrated that suppression of erythroid differentiation was associated with sharp inhibition of the expression of α-globin and γ-globin mRNA accumulation. Inhibition of accumulation of ζ-globin and ε-globin mRNAs was also observed. In addition, we provide in silico studies suggesting a direct interaction between SARS-CoV-2 Spike protein and Hb Portland, that is the major hemoglobin produced by K562 cells. This study thus provides information suggesting the need of great attention on possible alteration of hematopoietic parameters following SARS-CoV-2 infection and/or COVID-19 vaccination. |
| doi_str_mv | 10.1016/j.yexcr.2023.113853 |
| format | Article |
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The SARS-CoV-2 Spike protein (S-protein) plays an important role in the early phase of SARS-CoV-2 infection through efficient interaction with ACE2. The S-protein is produced by RNA-based COVID-19 vaccines, that were fundamental for the reduction of the viral spread within the population and the clinical severity of COVID-19. However, the S-protein has been hypothesized to be responsible for damaging cells of several tissues and for some important side effects of RNA-based COVID-19 vaccines. Considering the impact of COVID-19 and SARS-CoV-2 infection on the hematopoietic system, the aim of this study was to verify the effect of the BNT162b2 vaccine on erythroid differentiation of the human K562 cell line, that has been in the past intensively studied as a model system mimicking some steps of erythropoiesis. In this context, we focused on hemoglobin production and induced expression of embryo-fetal globin genes, that are among the most important features of K562 erythroid differentiation. We found that the BNT162b2 vaccine suppresses mithramycin-induced erythroid differentiation of K562 cells. Reverse-transcription-qPCR and Western blotting assays demonstrated that suppression of erythroid differentiation was associated with sharp inhibition of the expression of α-globin and γ-globin mRNA accumulation. Inhibition of accumulation of ζ-globin and ε-globin mRNAs was also observed. In addition, we provide in silico studies suggesting a direct interaction between SARS-CoV-2 Spike protein and Hb Portland, that is the major hemoglobin produced by K562 cells. This study thus provides information suggesting the need of great attention on possible alteration of hematopoietic parameters following SARS-CoV-2 infection and/or COVID-19 vaccination.</description><identifier>ISSN: 0014-4827</identifier><identifier>EISSN: 1090-2422</identifier><identifier>DOI: 10.1016/j.yexcr.2023.113853</identifier><identifier>PMID: 37944576</identifier><language>eng</language><publisher>United States</publisher><subject>BNT162 Vaccine ; COVID-19 - metabolism ; COVID-19 - prevention & control ; COVID-19 Vaccines - metabolism ; Erythroid Cells - metabolism ; Hemoglobins - metabolism ; Humans ; K562 Cells ; Leukemia, Erythroblastic, Acute - metabolism ; Plicamycin - metabolism ; Plicamycin - pharmacology ; RNA, Messenger - genetics ; SARS-CoV-2 - genetics ; SARS-CoV-2 - metabolism</subject><ispartof>Experimental cell research, 2023-12, Vol.433 (2), p.113853-113853, Article 113853</ispartof><rights>Copyright © 2023 The Authors. Published by Elsevier Inc. 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The SARS-CoV-2 Spike protein (S-protein) plays an important role in the early phase of SARS-CoV-2 infection through efficient interaction with ACE2. The S-protein is produced by RNA-based COVID-19 vaccines, that were fundamental for the reduction of the viral spread within the population and the clinical severity of COVID-19. However, the S-protein has been hypothesized to be responsible for damaging cells of several tissues and for some important side effects of RNA-based COVID-19 vaccines. Considering the impact of COVID-19 and SARS-CoV-2 infection on the hematopoietic system, the aim of this study was to verify the effect of the BNT162b2 vaccine on erythroid differentiation of the human K562 cell line, that has been in the past intensively studied as a model system mimicking some steps of erythropoiesis. In this context, we focused on hemoglobin production and induced expression of embryo-fetal globin genes, that are among the most important features of K562 erythroid differentiation. We found that the BNT162b2 vaccine suppresses mithramycin-induced erythroid differentiation of K562 cells. Reverse-transcription-qPCR and Western blotting assays demonstrated that suppression of erythroid differentiation was associated with sharp inhibition of the expression of α-globin and γ-globin mRNA accumulation. Inhibition of accumulation of ζ-globin and ε-globin mRNAs was also observed. In addition, we provide in silico studies suggesting a direct interaction between SARS-CoV-2 Spike protein and Hb Portland, that is the major hemoglobin produced by K562 cells. This study thus provides information suggesting the need of great attention on possible alteration of hematopoietic parameters following SARS-CoV-2 infection and/or COVID-19 vaccination.</description><subject>BNT162 Vaccine</subject><subject>COVID-19 - metabolism</subject><subject>COVID-19 - prevention & control</subject><subject>COVID-19 Vaccines - metabolism</subject><subject>Erythroid Cells - metabolism</subject><subject>Hemoglobins - metabolism</subject><subject>Humans</subject><subject>K562 Cells</subject><subject>Leukemia, Erythroblastic, Acute - metabolism</subject><subject>Plicamycin - metabolism</subject><subject>Plicamycin - pharmacology</subject><subject>RNA, Messenger - genetics</subject><subject>SARS-CoV-2 - genetics</subject><subject>SARS-CoV-2 - metabolism</subject><issn>0014-4827</issn><issn>1090-2422</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2023</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNo9kd1uFCEUx4nR2LX6BCaGS29YOTAfzGXd1I_YaGJXbwnDHLqsM8MKM6bzNj6BD-GTyXZbr4DD-f8g50fIS-Br4FC92a8XvLVxLbiQawCpSvmIrIA3nIlCiMdkxTkUrFCiPiPPUtpzzpWC6ik5k3VTFGVdrcif7Q6pGSfPri--XrNN-M4Efft5C5VoBf1lrPUj0jQfDhFTwkQHP-2iGZZcZ37sZosdxbjkYvAd7bxzGDHzzOTDmMn59vYuezwGR3Fo4xKYw8n09KYPrR_pDY6ZnDe7eTDjA67H-QcO3tBPZSX-_rbY9-k5eeJMn_DF_XpOvr273G4-sKsv7z9uLq6YlZxPDIQrQGKHbdPVYEE0beVK5cApw2XnABVKW9WgTJ5C3VZKFLYwZaOULVGiPCevT9xDDD9nTJMefDr-wIwY5qSFUo3IE6wht8pTq40hpYhOH6IfTFw0cH0Upff6TpQ-itInUTn16v6BuR2w-595MCP_AaytlAg</recordid><startdate>20231215</startdate><enddate>20231215</enddate><creator>Zurlo, Matteo</creator><creator>Gasparello, Jessica</creator><creator>Verona, Marco</creator><creator>Papi, Chiara</creator><creator>Cosenza, Lucia Carmela</creator><creator>Finotti, Alessia</creator><creator>Marzaro, Giovanni</creator><creator>Gambari, Roberto</creator><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>7X8</scope><orcidid>https://orcid.org/0000-0001-9242-1766</orcidid><orcidid>https://orcid.org/0000-0002-6131-3727</orcidid><orcidid>https://orcid.org/0000-0002-2949-7191</orcidid></search><sort><creationdate>20231215</creationdate><title>The anti-SARS-CoV-2 BNT162b2 vaccine suppresses mithramycin-induced erythroid differentiation and expression of embryo-fetal globin genes in human erythroleukemia K562 cells</title><author>Zurlo, Matteo ; 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In this context, we focused on hemoglobin production and induced expression of embryo-fetal globin genes, that are among the most important features of K562 erythroid differentiation. We found that the BNT162b2 vaccine suppresses mithramycin-induced erythroid differentiation of K562 cells. Reverse-transcription-qPCR and Western blotting assays demonstrated that suppression of erythroid differentiation was associated with sharp inhibition of the expression of α-globin and γ-globin mRNA accumulation. Inhibition of accumulation of ζ-globin and ε-globin mRNAs was also observed. In addition, we provide in silico studies suggesting a direct interaction between SARS-CoV-2 Spike protein and Hb Portland, that is the major hemoglobin produced by K562 cells. 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| ispartof | Experimental cell research, 2023-12, Vol.433 (2), p.113853-113853, Article 113853 |
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| source | MEDLINE; ScienceDirect Journals (5 years ago - present) |
| subjects | BNT162 Vaccine COVID-19 - metabolism COVID-19 - prevention & control COVID-19 Vaccines - metabolism Erythroid Cells - metabolism Hemoglobins - metabolism Humans K562 Cells Leukemia, Erythroblastic, Acute - metabolism Plicamycin - metabolism Plicamycin - pharmacology RNA, Messenger - genetics SARS-CoV-2 - genetics SARS-CoV-2 - metabolism |
| title | The anti-SARS-CoV-2 BNT162b2 vaccine suppresses mithramycin-induced erythroid differentiation and expression of embryo-fetal globin genes in human erythroleukemia K562 cells |
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