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Serine Protease Inh...
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Rosendal, EbbaUmeå universitet,Institutionen för klinisk mikrobiologi,Molekylär Infektionsmedicin, Sverige (MIMS),Umeå Univ, Dept Clin Microbiol, Umeå, Sweden.;Umeå Univ, Lab Mol Infect Med Sweden MIMS, Umeå, Sweden.
(author)
Serine Protease Inhibitors Restrict Host Susceptibility to SARS-CoV-2 Infections
- Article/chapterEnglish2022
Publisher, publication year, extent ...
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American Society for Microbiology,2022
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printrdacarrier
Numbers
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LIBRIS-ID:oai:DiVA.org:su-205256
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https://urn.kb.se/resolve?urn=urn:nbn:se:su:diva-205256URI
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https://doi.org/10.1128/mbio.00892-22DOI
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https://urn.kb.se/resolve?urn=urn:nbn:se:umu:diva-203186URI
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http://kipublications.ki.se/Default.aspx?queryparsed=id:149646750URI
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https://urn.kb.se/resolve?urn=urn:nbn:se:uu:diva-485470URI
Supplementary language notes
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Language:English
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Summary in:English
Part of subdatabase
Classification
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Subject category:ref swepub-contenttype
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Subject category:art swepub-publicationtype
Notes
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The coronavirus disease 2019, COVID-19, is a complex disease with a wide range of symptoms from asymptomatic infections to severe acute respiratory syndrome with lethal outcome. Individual factors such as age, sex, and comorbidities increase the risk for severe infections, but other aspects, such as genetic variations, are also likely to affect the susceptibility to SARS-CoV-2 infection and disease severity. Here, we used a human 3D lung cell model based on primary cells derived from multiple donors to identity host factors that regulate SARS-CoV-2 infection. With a transcriptomics-based approach, we found that less susceptible donors show a higher expression level of serine protease inhibitors SERPINA1, SERPINE1, and SERPINE2, identifying variation in cellular serpin levels as restricting host factors for SARS-CoV-2 infection. We pinpoint their antiviral mechanism of action to inhibition of the cellular serine protease, TMPRSS2, thereby preventing cleavage of the viral spike protein and TMPRSS2-mediated entry into the target cells. By means of single-cell RNA sequencing, we further locate the expression of the individual serpins to basal, ciliated, club, and goblet cells. Our results add to the importance of genetic variations as determinants for SARS-CoV-2 susceptibility and suggest that genetic deficiencies of cellular serpins might represent risk factors for severe COVID-19. Our study further highlights TMPRSS2 as a promising target for antiviral intervention and opens the door for the usage of locally administered serpins as a treatment against COVID-19.
Subject headings and genre
Added entries (persons, corporate bodies, meetings, titles ...)
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Mihai, Ionut SebastianUmeå universitet,Molekylär Infektionsmedicin, Sverige (MIMS),Institutionen för molekylärbiologi (Medicinska fakulteten),National Clinical Research School in Chronic Inflammatory Diseases (NCRSCID), Karolinska Institutet, Solna, Sweden,Umeå Univ, Lab Mol Infect Med Sweden MIMS, Umeå, Sweden.;Umeå Univ, Dept Mol Biol, Umeå, Sweden.;Umeå Univ, Ind Doctoral Sch, Umeå, Sweden.;Karolinska Inst, Natl Clin Res Sch Chron Inflammatory Dis NCRSCID, Solna, Sweden.(Swepub:umu)iose0003
(author)
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Becker, MiriamUmeå universitet,Institutionen för klinisk mikrobiologi,Wallenberg centrum för molekylär medicin vid Umeå universitet (WCMM),Institute for Experimental Virology, TWINCORE, Centre for Experimental and Clinical Infection Research, a joint venture between The Medical School Hannover, The Helmholtz Centre for Infection Research, Hannover, Germany; Department of Biochemistry & Research Center for Emerging Infections and Zoonoses (RIZ), University of Veterinary Medicine Hannover, Hannover, Germany,Umeå Univ, Dept Clin Microbiol, Umeå, Sweden.;Ctr Expt & Clin Infect Res, Joint Venture Med Sch Hannover, Inst Expt Virol, TWINCORE, Hannover, Germany.;Helmholtz Ctr Infect Res, Hannover, Germany.;Univ Vet Med Hannover, Dept Biochem, Hannover, Germany.;Univ Vet Med Hannover, Res Ctr Emerging Infect & Zoonoses RIZ, Hannover, Germany.;Umeå Univ, Wallenberg Ctr Mol Med WCMM, Umeå, Sweden.(Swepub:umu)mibe0174
(author)
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Das, DebojyotiUmeå universitet,Molekylär Infektionsmedicin, Sverige (MIMS),Institutionen för molekylärbiologi (Medicinska fakulteten),Umeå Univ, Lab Mol Infect Med Sweden MIMS, Umeå, Sweden.;Umeå Univ, Dept Mol Biol, Umeå, Sweden.,Umeå Univ, Sect Med, Dept Publ Hlth & Clin Med, Umeå, Sweden.;CBRN Def & Secur, Swedish Def Res Agcy, Umeå, Sweden.(Swepub:umu)deda0016
(author)
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Frängsmyr, LarsUmeå universitet,Institutionen för klinisk mikrobiologi,Umeå Univ, Dept Clin Microbiol, Umeå, Sweden.(Swepub:umu)lacfrr79
(author)
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Persson, B. DavidUmeå universitet,Institutionen för klinisk mikrobiologi,Swedish National Veterinary Institute (SVA), Uppsala, Sweden,Umeå Univ, Dept Clin Microbiol, Umeå, Sweden.;Swedish Natl Vet Inst SVA, Uppsala, Sweden.(Swepub:umu)peda8601
(author)
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Rankin, GregoryUmeå universitet,Avdelningen för medicin,Swedish Defence Research Agency, CBRN Defence and Security, Umeå, Sweden(Swepub:umu)grdo0001
(author)
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Gröning, RemigiusUmeå universitet,Institutionen för klinisk mikrobiologi,Umeå Univ, Dept Clin Microbiol, Umeå, Sweden.(Swepub:umu)regr0024
(author)
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Trygg, JohanUmeå universitet,Kemiska institutionen,Sartorius Corporate Research, Umeå, Sweden,Umeå Univ, Dept Chem, Umeå, Sweden.;Sartorius Corp Res, Umeå, Sweden.(Swepub:umu)jotr0001
(author)
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Forsell, MattiasUmeå universitet,Institutionen för klinisk mikrobiologi,Umeå Univ, Dept Clin Microbiol, Umeå, Sweden.(Swepub:umu)mafo0173
(author)
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Ankarklev, JohanUppsala universitet,Stockholms universitet,Institutionen för molekylär biovetenskap, Wenner-Grens institut,Department of Molecular Biosciences, The Wenner-Gren Institute, Stockholm University, Stockholm, Sweden; Microbial Single Cell Genomics Facility, SciLifeLab, Biomedical Center (BMC) Uppsala University, Uppsala, Sweden,Science for Life Laboratory, SciLifeLab,Institutionen för cell- och molekylärbiologi,Stockholm Univ, Wenner Gren Inst, Dept Mol Biosci, Stockholm, Sweden.(Swepub:uu)joank425
(author)
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Blomberg, Anders,1961-Umeå universitet,Avdelningen för medicin,Umeå Univ, Sect Med, Dept Publ Hlth & Clin Med, Umeå, Sweden.(Swepub:umu)anbl0001
(author)
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Henriksson, JohanUmeå universitet,Molekylär Infektionsmedicin, Sverige (MIMS),Institutionen för molekylärbiologi (Medicinska fakulteten),Umeå Univ, Lab Mol Infect Med Sweden MIMS, Umeå, Sweden.;Umeå Univ, Dept Mol Biol, Umeå, Sweden.(Swepub:umu)johe6219
(author)
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Överby, Anna K.Umeå universitet,Molekylär Infektionsmedicin, Sverige (MIMS),Institutionen för klinisk mikrobiologi,Umeå Univ, Dept Clin Microbiol, Umeå, Sweden.;Umeå Univ, Lab Mol Infect Med Sweden MIMS, Umeå, Sweden.(Swepub:umu)anaovy99
(author)
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Lenman, Annasara,1983-Umeå universitet,Institutionen för klinisk mikrobiologi,Umeå Univ, Dept Clin Microbiol, Umeå, Sweden.(Swepub:umu)anamad03
(author)
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Umeå universitetInstitutionen för klinisk mikrobiologi
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In:mBio: American Society for Microbiology13:32161-21292150-7511
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Rosendal, Ebba
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Mihai, Ionut Seb ...
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Becker, Miriam
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Das, Debojyoti
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Frängsmyr, Lars
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Persson, B. Davi ...
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Rankin, Gregory
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Gröning, Remigiu ...
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Trygg, Johan
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Ankarklev, Johan
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Henriksson, Joha ...
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