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Epigenetic rewiring of pathways related to odour perception in immune cells exposed to SARS-CoV-2 in vivo and in vitro
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- Huoman, Johanna (author)
- Linköpings universitet,Avdelningen för inflammation och infektion,Medicinska fakulteten,Univ Hosp Bonn, Germany
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- Sayyab, Shumaila (author)
- Linköpings universitet,Avdelningen för inflammation och infektion,Medicinska fakulteten
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- Apostolou, Eirini (author)
- Linköpings universitet,Avdelningen för cellbiologi,Medicinska fakulteten
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- (creator_code:org_t)
- 2022-06-26
- 2022
- English.
- In: Epigenetics. - New York, NY, United States : Taylor & Francis. - 1559-2294 .- 1559-2308. ; 17:13, s. 1875-1891
- Journal article (peer-reviewed)
Abstract
Subject headings
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- A majority of SARS-CoV-2 recoverees develop only mild-to-moderate symptoms, while some remain completely asymptomatic. Although viruses, including SARS-CoV-2, may evade host immune responses by epigenetic mechanisms including DNA methylation, little is known about whether these modifications are important in defence against and healthy recovery from COVID-19 in the host. To this end, epigenome-wide DNA methylation patterns from COVID-19 convalescents were compared to uninfected controls from before and after the pandemic. Peripheral blood mononuclear cell (PBMC) DNA was extracted from uninfected controls, COVID-19 convalescents, and symptom-free individuals with SARS-CoV-2-specific T cell-responses, as well as from PBMCs stimulated in vitro with SARS-CoV-2. Subsequently, the Illumina MethylationEPIC 850K array was performed, and statistical/bioinformatic analyses comprised differential DNA methylation, pathway over-representation, and module identification analyses. Differential DNA methylation patterns distinguished COVID-19 convalescents from uninfected controls, with similar results in an experimental SARS-CoV-2 infection model. A SARS-CoV-2-induced module was identified in vivo, comprising 66 genes of which six (TP53, INS, HSPA4, SP1, ESR1, and FAS) were present in corresponding in vitro analyses. Over-representation analyses revealed involvement in Wnt, muscarinic acetylcholine receptor signalling, and gonadotropin-releasing hormone receptor pathways. Furthermore, numerous differentially methylated and network genes from both settings interacted with the SARS-CoV-2 interactome. Altered DNA methylation patterns of COVID-19 convalescents suggest recovery from mild-to-moderate SARS-CoV-2 infection leaves longstanding epigenetic traces. Both in vitro and in vivo exposure caused epigenetic modulation of pathways thataffect odour perception. Future studies should determine whether this reflects host-induced protective antiviral defense or targeted viral hijacking to evade host defence.
Subject headings
- LANTBRUKSVETENSKAPER -- Veterinärmedicin -- Medicinsk biovetenskap (hsv//swe)
- AGRICULTURAL SCIENCES -- Veterinary Science -- Medical Bioscience (hsv//eng)
Keyword
- SARS-CoV-2; mild-to-moderate; PBMC; DNA methylation; in vitro stimulation; module identification; network analysis; interactome
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- Karlsson, Lovisa
- Porcile, Lucas
- Rizwan, Muhammad
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- Sharma, Sumit
- Das, Jyotirmoy
- Rosén, Anders
- Lerm, Maria
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- Epigenetics
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