dc.contributor.author
Los, Bruna
dc.contributor.author
Preußner, Marco
dc.contributor.author
Eschke, Kathrin
dc.contributor.author
Vidal, Ricardo Martin
dc.contributor.author
Abdelgawad, Azza
dc.contributor.author
Olofsson, Didrik
dc.contributor.author
Keiper, Sandra
dc.contributor.author
Paulo-Pedro, Margarida
dc.contributor.author
Grindel, Alica
dc.contributor.author
Meinke, Stefan
dc.contributor.author
Trimpert, Jakob
dc.contributor.author
Heyd, Florian
dc.date.accessioned
2022-08-05T11:15:26Z
dc.date.available
2022-08-05T11:15:26Z
dc.identifier.uri
https://refubium.fu-berlin.de/handle/fub188/35753
dc.identifier.uri
http://dx.doi.org/10.17169/refubium-35468
dc.description.abstract
Antiviral innate immunity represents the first defense against invading viruses and is key to control viral infections, including SARS-CoV-2. Body temperature is an omnipresent variable but was neglected when addressing host defense mechanisms and susceptibility to SARS-CoV-2 infection. Here, we show that increasing temperature in a 1.5°C window, between 36.5 and 38°C, strongly increases the expression of genes in two branches of antiviral immunity, nitric oxide production and type I interferon response. We show that alternative splicing coupled to nonsense-mediated decay decreases STAT2 expression in colder conditions and suggest that increased STAT2 expression at elevated temperature induces the expression of diverse antiviral genes and SARS-CoV-2 restriction factors. This cascade is activated in a remarkably narrow temperature range below febrile temperature, which reflects individual, circadian and age-dependent variation. We suggest that decreased body temperature with aging contributes to reduced expression of antiviral genes in older individuals. Using cell culture and in vivo models, we show that higher body temperature correlates with reduced SARS-CoV-2 replication, which may affect the different vulnerability of children versus seniors toward severe SARS-CoV-2 infection. Altogether, our data connect body temperature and pre-mRNA processing to provide new mechanistic insight into the regulation of antiviral innate immunity.
en
dc.format.extent
17 Seiten
dc.rights.uri
https://creativecommons.org/licenses/by/4.0/
dc.subject
Gene Regulation
en
dc.subject.ddc
600 Technik, Medizin, angewandte Wissenschaften::610 Medizin und Gesundheit::616 Krankheiten
dc.title
Body temperature variation controls pre-mRNA processing and transcription of antiviral genes and SARS-CoV-2 replication
dc.type
Wissenschaftlicher Artikel
dcterms.bibliographicCitation.doi
10.1093/nar/gkac513
dcterms.bibliographicCitation.journaltitle
Nucleic Acids Research
dcterms.bibliographicCitation.number
12
dcterms.bibliographicCitation.pagestart
6769
dcterms.bibliographicCitation.pageend
6785
dcterms.bibliographicCitation.volume
50
dcterms.bibliographicCitation.url
https://doi.org/10.1093/nar/gkac513
refubium.affiliation
Biologie, Chemie, Pharmazie
refubium.affiliation
Veterinärmedizin
refubium.affiliation.other
Institut für Chemie und Biochemie

refubium.affiliation.other
Institut für Virologie

refubium.resourceType.isindependentpub
no
dcterms.accessRights.openaire
open access
dcterms.isPartOf.eissn
1362-4962
refubium.resourceType.provider
WoS-Alert