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Status: Bibliographieeintrag

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Verfasst von:Khanal, Rajendra [VerfasserIn]   i
 Heinen, Natalie [VerfasserIn]   i
 Bogomolova, Alexandra [VerfasserIn]   i
 Meister, Toni L. [VerfasserIn]   i
 Herrmann, Simon T. [VerfasserIn]   i
 Westhoven, Saskia [VerfasserIn]   i
 Nocke, Maximilian K. [VerfasserIn]   i
 Todt, Daniel [VerfasserIn]   i
 Jockenhövel, Freya [VerfasserIn]   i
 Klein, Isabel M. [VerfasserIn]   i
 Hartmann, Laura [VerfasserIn]   i
 Vondran, Florian W. R. [VerfasserIn]   i
 Steinmann, Eike [VerfasserIn]   i
 Zimmer, Gert [VerfasserIn]   i
 Ott, Michael [VerfasserIn]   i
 Brown, Richard J. P. [VerfasserIn]   i
 Sharma, Amar Deep [VerfasserIn]   i
 Pfaender, Stephanie [VerfasserIn]   i
Titel:MicroRNAs modulate SARS-CoV-2 infection of primary human hepatocytes by regulating the entry factors ACE2 and TMPRSS2
Verf.angabe:Rajendra Khanal, Natalie Heinen, Alexandra Bogomolova, Toni L. Meister, Simon T. Herrmann, Saskia Westhoven, Maximilian K. Nocke, Daniel Todt, Freya Jockenhövel, Isabel M. Klein, Laura Hartmann, Florian W. R. Vondran, Eike Steinmann, Gert Zimmer, Michael Ott, Richard J. P. Brown, Amar Deep Sharma, Stephanie Pfaender
E-Jahr:2024
Jahr:November 2024
Umfang:13 S.
Illustrationen:Illustrationen
Fussnoten:Zuerst veröffentlicht: 22. August 2024 ; Gesehen am 07.11.2024
Titel Quelle:Enthalten in: Liver international
Ort Quelle:Oxford : Wiley-Blackwell, 2003
Jahr Quelle:2024
Band/Heft Quelle:44(2024), 11 vom: Nov., Seite 2983-2995
ISSN Quelle:1478-3231
Abstract:Background and Aims Severe acute respiratory syndrome coronavirus (SARS-CoV-2) preferentially infects the respiratory tract; however, several studies have implicated a multi-organ involvement. Hepatic dysfunctions caused by SARS-CoV-2 infection have been increasingly recognized and described to correlate with disease severity. To elucidate molecular factors that could contribute towards hepatic infection, we concentrated on microRNAs (miRNAs), a class of small non-coding RNAs that modulate various cellular processes and which are reported to be differentially regulated during liver injury. We aimed to study the infection of primary human hepatocytes (PHH) with SARS-CoV-2 and to evaluate the potential of miRNAs for modulating viral infection. Methods We analysed liver autopsies from a coronavirus disease 19 (COVID-19)-positive cohort for the presence of viral RNA using Nanopore sequencing. PHH were used for the infection with SARS-CoV-2. The candidate miRNAs targeting angiotensin converting enzyme 2 (ACE2) and transmembrane serine protease 2 (TMPRSS2) were identified using in silico approaches. To discover the potential regulatory mechanism, transfection experiments, qRT-PCRs, western blots and luciferase reporter assays were performed. Results We could detect SARS-CoV-2 RNA in COVID-19-positive liver autopsies. We show that PHH express ACE2 and TMPRSS2 and can be readily infected with SARS-CoV-2, resulting in robust replication. Transfection of selected miRNA mimics reduced SARS-CoV-2 receptor expression and SARS-CoV-2 burden in PHH. In silico and biochemical analyses supported a potential direct binding of miR-141-3p to the SARS-CoV-2 genome. Conclusion We confirm that PHH are susceptible to SARS-CoV-2 infection and demonstrate selected miRNAs targeting SARS-CoV-2 entry factors and/or the viral genome reduce viral loads. These data provide novel insights into hepatic susceptibility to SARS-CoV-2 and associated dysfunctions in COVID-19.
DOI:doi:10.1111/liv.16079
URL:Bitte beachten Sie: Dies ist ein Bibliographieeintrag. Ein Volltextzugriff für Mitglieder der Universität besteht hier nur, falls für die entsprechende Zeitschrift/den entsprechenden Sammelband ein Abonnement besteht oder es sich um einen OpenAccess-Titel handelt.

kostenfrei: Volltext: https://doi.org/10.1111/liv.16079
 kostenfrei: Volltext: https://onlinelibrary.wiley.com/doi/abs/10.1111/liv.16079
 DOI: https://doi.org/10.1111/liv.16079
Datenträger:Online-Ressource
Sprache:eng
Sach-SW:ACE2
 COVID-19
 liver
 microRNAs
 non-coding RNAs
 primary human hepatocytes
 SARS-CoV-2
 TMPRSS2
K10plus-PPN:1907902562
Verknüpfungen:→ Zeitschrift

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