Chronic Exposure to the Food Additive tBHQ Modulates Expression of Genes Related to SARS-CoV-2 and Influenza Viruses

Background. <i>tert</i>-butylhydroquinone (tBHQ) is an antioxidant commonly used as a food additive. Studies suggest that tBHQ could modulate immune responses to influenza and SARS-CoV-2 infection. In our transcriptomic analysis we explored the molecular mechanisms behind tBHQ’s modulato...

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Main Authors: Krisztina Németh, Peter Petschner, Krisztina Pálóczi, Nóra Fekete, Éva Pállinger, Edit I. Buzás, Viola Tamási
Format: Article
Language:English
Published: MDPI AG 2022-04-01
Series:Life
Subjects:
Online Access:https://www.mdpi.com/2075-1729/12/5/642
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author Krisztina Németh
Peter Petschner
Krisztina Pálóczi
Nóra Fekete
Éva Pállinger
Edit I. Buzás
Viola Tamási
author_facet Krisztina Németh
Peter Petschner
Krisztina Pálóczi
Nóra Fekete
Éva Pállinger
Edit I. Buzás
Viola Tamási
author_sort Krisztina Németh
collection DOAJ
description Background. <i>tert</i>-butylhydroquinone (tBHQ) is an antioxidant commonly used as a food additive. Studies suggest that tBHQ could modulate immune responses to influenza and SARS-CoV-2 infection. In our transcriptomic analysis we explored the molecular mechanisms behind tBHQ’s modulatory properties and the relationships to respiratory viral infections. Methods. tBHQ was administered <i>per os</i> to BALB/c mice (1.5% [<i>w</i>/<i>w</i>]) for 20 days. Splenic T cells were isolated with magnetic separation and subjected to transcriptomic analysis. Gene-set enrichment analysis and g:Profiler was conducted to provide a functional interpretation of significantly changed genes. Further analysis for AHR/NRF2 binding sites was performed with GeneHancer. Results. In CD4<sup>+</sup> cells, we found significantly altered expression of 269 genes by tBHQ. Of them, many had relevance in influenza infection such as genes responsible for virus entry (<i>Anxa1/2</i>, <i>Cd14</i>), interferon signaling (<i>Dusp10</i>, <i>Tnfsf13</i>), or prostaglandin synthesis (Ptgs1/2). In SARS-CoV-2 infections, interferon signaling (<i>Ifitm</i>1), proteolytic enzymes (<i>CtsB</i>), and also cell-surface proteins (<i>Cd14</i>, <i>Cd151</i>) were among the prominent alterations after tBHQ exposure. Of these genes, many had one or more binding sites for AHR and NRF2, two major xenosensors triggered by tBHQ. Conclusions. Our results strongly suggest that a common food additive, tBHQ, can modulate virus-dependent processes in both influenza and SARS-CoV-2 infections.
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spelling doaj.art-bb8cbc201c014734a11553f77ce9f6852023-11-23T11:49:15ZengMDPI AGLife2075-17292022-04-0112564210.3390/life12050642Chronic Exposure to the Food Additive tBHQ Modulates Expression of Genes Related to SARS-CoV-2 and Influenza VirusesKrisztina Németh0Peter Petschner1Krisztina Pálóczi2Nóra Fekete3Éva Pállinger4Edit I. Buzás5Viola Tamási6Department of Genetics, Cell- and Immunobiology, Semmelweis University, 1089 Budapest, HungaryDepartment of Pharmacodynamics, Semmelweis University, 1089 Budapest, HungaryDepartment of Genetics, Cell- and Immunobiology, Semmelweis University, 1089 Budapest, HungaryDepartment of Genetics, Cell- and Immunobiology, Semmelweis University, 1089 Budapest, HungaryDepartment of Genetics, Cell- and Immunobiology, Semmelweis University, 1089 Budapest, HungaryDepartment of Genetics, Cell- and Immunobiology, Semmelweis University, 1089 Budapest, HungaryDepartment of Molecular Biology, Institute of Biochemistry and Molecular Biology, Semmelweis University, 1094 Budapest, HungaryBackground. <i>tert</i>-butylhydroquinone (tBHQ) is an antioxidant commonly used as a food additive. Studies suggest that tBHQ could modulate immune responses to influenza and SARS-CoV-2 infection. In our transcriptomic analysis we explored the molecular mechanisms behind tBHQ’s modulatory properties and the relationships to respiratory viral infections. Methods. tBHQ was administered <i>per os</i> to BALB/c mice (1.5% [<i>w</i>/<i>w</i>]) for 20 days. Splenic T cells were isolated with magnetic separation and subjected to transcriptomic analysis. Gene-set enrichment analysis and g:Profiler was conducted to provide a functional interpretation of significantly changed genes. Further analysis for AHR/NRF2 binding sites was performed with GeneHancer. Results. In CD4<sup>+</sup> cells, we found significantly altered expression of 269 genes by tBHQ. Of them, many had relevance in influenza infection such as genes responsible for virus entry (<i>Anxa1/2</i>, <i>Cd14</i>), interferon signaling (<i>Dusp10</i>, <i>Tnfsf13</i>), or prostaglandin synthesis (Ptgs1/2). In SARS-CoV-2 infections, interferon signaling (<i>Ifitm</i>1), proteolytic enzymes (<i>CtsB</i>), and also cell-surface proteins (<i>Cd14</i>, <i>Cd151</i>) were among the prominent alterations after tBHQ exposure. Of these genes, many had one or more binding sites for AHR and NRF2, two major xenosensors triggered by tBHQ. Conclusions. Our results strongly suggest that a common food additive, tBHQ, can modulate virus-dependent processes in both influenza and SARS-CoV-2 infections.https://www.mdpi.com/2075-1729/12/5/642tBHQSARS-CoV-2influenzaCD4T cellsfood additive
spellingShingle Krisztina Németh
Peter Petschner
Krisztina Pálóczi
Nóra Fekete
Éva Pállinger
Edit I. Buzás
Viola Tamási
Chronic Exposure to the Food Additive tBHQ Modulates Expression of Genes Related to SARS-CoV-2 and Influenza Viruses
Life
tBHQ
SARS-CoV-2
influenza
CD4
T cells
food additive
title Chronic Exposure to the Food Additive tBHQ Modulates Expression of Genes Related to SARS-CoV-2 and Influenza Viruses
title_full Chronic Exposure to the Food Additive tBHQ Modulates Expression of Genes Related to SARS-CoV-2 and Influenza Viruses
title_fullStr Chronic Exposure to the Food Additive tBHQ Modulates Expression of Genes Related to SARS-CoV-2 and Influenza Viruses
title_full_unstemmed Chronic Exposure to the Food Additive tBHQ Modulates Expression of Genes Related to SARS-CoV-2 and Influenza Viruses
title_short Chronic Exposure to the Food Additive tBHQ Modulates Expression of Genes Related to SARS-CoV-2 and Influenza Viruses
title_sort chronic exposure to the food additive tbhq modulates expression of genes related to sars cov 2 and influenza viruses
topic tBHQ
SARS-CoV-2
influenza
CD4
T cells
food additive
url https://www.mdpi.com/2075-1729/12/5/642
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