Navigation überspringen
Universitätsbibliothek Heidelberg
Status: Bibliographieeintrag

Verfügbarkeit
Standort: ---
Exemplare: ---
heiBIB
 Online-Ressource
Verfasst von:Zhang, Zhenfeng [VerfasserIn]   i
 Ni, Yi [VerfasserIn]   i
 Lempp, Florian A. [VerfasserIn]   i
 Walter, Lisa [VerfasserIn]   i
 Mutz, Pascal [VerfasserIn]   i
 Bartenschlager, Ralf [VerfasserIn]   i
 Urban, Stephan [VerfasserIn]   i
Titel:Hepatitis D virus-induced interferon response and administered interferons control cell division-mediated virus spread
Verf.angabe:Zhenfeng Zhang, Yi Ni, Florian A. Lempp, Lisa Walter, Pascal Mutz, Ralf Bartenschlager, Stephan Urban
E-Jahr:2022
Jahr:16 September 2022
Umfang:10 S.
Fussnoten:Online verfügbar 28. Mai 2022, Artikelversion 16 September 2022 ; Gesehen am 17.01.2023
Titel Quelle:Enthalten in: Journal of hepatology
Ort Quelle:Amsterdam [u.a.] : Elsevier Science, 1985
Jahr Quelle:2022
Band/Heft Quelle:77(2022), 4, Seite 957-966
ISSN Quelle:1600-0641
Abstract:Background & aims - Besides HBV-dependent de novo infection, cell division-mediated spread contributes to HDV persistence and dampens the effect of antivirals that abrogate de novo infection. Nonetheless, the combination of these antivirals with interferons (IFNs) showed strong synergism in recent clinical trials, implying a complementary mode-of-action of IFNs. Therefore, we investigated the effect of IFN response on cell division-mediated HDV spread. - Methods - Cells infected with HDV were passaged to undergo cell division. The effect of the IFN response was evaluated by blocking HDV-induced IFN activation, by applying different IFN treatment regimens, and by adjusting HDV infection doses. - Results - Cell division-mediated HDV spread was highly efficient following infection of HuH7NTCP cells (defective in IFN production), but profoundly restricted in infected IFN-competent HepaRGNTCP cells. Treatment with IFN-α/-λ1 inhibited HDV spread in dividing HuH7NTCP cells, but exhibited a marginal effect on HDV replication in resting cells. Blocking the HDV-induced IFN response with the JAK1/2 inhibitor ruxolitinib or knocking down MDA5 augmented HDV spread in dividing HepaRGNTCP cells. The virus-induced IFN response also destabilized HDV RNA in dividing cells. Moreover, the effect of exogenous IFNs on cell division-mediated HDV spread was more pronounced at low multiplicities of infection with weak virus-induced IFN responses. - Conclusions - Both HDV-induced IFN response and exogenous IFN treatment suppress cell division-mediated HDV spread, presumably through acceleration of HDV RNA decay. Our findings demonstrate a novel mode-of-action of IFN, explain the more pronounced effect of IFN therapy in patients with lower HDV serum RNA levels, and provide insights for the development of combination therapies. - Lay summary - Chronic hepatitis D is a major health problem. The causative pathogen hepatitis D virus (HDV) can propagate through viral particle-mediated infection and the division of infected cells. Although viral particle-dependent infection can be blocked by recently developed drugs, therapies addressing the cell division route have not been reported. Taking advantage of relevant cell culture models, we demonstrate that the widely used immune modulator interferon can efficiently suppress HDV spread through cell division. This work unveils a new function of interferon and sheds light on potentially curative combination therapies.
DOI:doi:10.1016/j.jhep.2022.05.023
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.

Volltext: https://doi.org/10.1016/j.jhep.2022.05.023
 Volltext: https://www.sciencedirect.com/science/article/pii/S0168827822003385
 DOI: https://doi.org/10.1016/j.jhep.2022.05.023
Datenträger:Online-Ressource
Sprache:eng
Sach-SW:cell division-mediated spread
 hepatitis B virus
 hepatitis D virus
 interferon therapy
 viral persistence
 virus-induced interferon response
K10plus-PPN:1831210746
Verknüpfungen:→ Zeitschrift

Permanenter Link auf diesen Titel (bookmarkfähig):  https://katalog.ub.uni-heidelberg.de/titel/69006835   QR-Code
zum Seitenanfang