Navigation überspringen
Universitätsbibliothek Heidelberg
Status: Bibliographieeintrag

Verfügbarkeit
Standort: ---
Exemplare: ---
heiBIB
 Online-Ressource
Verfasst von:Costa, Rui [VerfasserIn]   i
 Schenk, Christian [VerfasserIn]   i
 Lohmann, Volker [VerfasserIn]   i
Titel:SEC14L2, a lipid-binding protein, regulates HCV replication in culture with inter- and intra-genotype variations
Verf.angabe:Rui Costa, Daniel Todt, Francisco Zapatero-Belinchón, Christian Schenk, Olympia E. Anastasiou, Andreas Walker, Barbara Hertel, Lejla Timmer, Denisa Bojkova, Maren Ruckert, Christoph Sarrazin, Jörg Timm, Volker Lohmann, Michael P. Manns, Eike Steinmann, Thomas von Hahn, Sandra Ciesek
Jahr:2019
Jahr des Originals:2018
Umfang:12 S.
Fussnoten:Available online 23 November 2018 ; Gesehen am 05.04.2019
Titel Quelle:Enthalten in: Journal of hepatology
Ort Quelle:Amsterdam [u.a.] : Elsevier Science, 1985
Jahr Quelle:2019
Band/Heft Quelle:70(2019), 4, Seite 603-614
ISSN Quelle:1600-0641
Abstract:Background & Aims - The lipid-binding protein, SEC14L2, is crucial for the efficient viral replication of clinical hepatitis C virus (HCV) isolates in cell culture. Given the role of SEC14L2 in HCV replication, we aimed to study a large number of HCV positive sera carrying genotypes 1-4, to identify viral factors associated with efficient replication in culture. Additionally, we investigated whether 13 single nucleotide polymorphisms (SNPs) of SEC14L2 have an impact on RNA replication of naturally occurring HCV isolates. - Methods - We generated Huh-7.5 cell lines overexpressing SEC14L2 or 13 coding SNPs and tested 73 different HCV positive sera for in vitro replication. Furthermore, we genotyped a cohort of 262 patients with chronic HCV for the common SNP (rs757660) and investigated its effect on the clinical phenotype. - Results - HCV isolates from genotype 1, 2, 3 and 4 replicate in Huh-7.5 cells overexpressing SEC14L2. Interestingly, only subgenomic replicons from genotypes 1 and 3 showed enhanced replication whereas genotypes 2 and 4 remained unaffected. Furthermore, replication was independent of viral load. Importantly, all tested SNPs supported HCV RNA replication in vitro, while 1 SNP was associated with decreased SEC1L2 expression and viral RNA. All SNPs exhibited comparable cellular cholesterol and vitamin E abundance in naïve Huh-7.5 cells. - Conclusions - This large screen of natural HCV isolates of 4 genotypes underscores the relevance of SEC14L2 as an in vitro HCV host factor. Additionally, SEC14L2 variants appear to recapitulate the wild-type enhancement of HCV replication. Variant rs191341134 showed a decreased effect due to lowered stability, whereas variant rs757660, a high prevalence mutant, showed a similar phenotype to the wild-type. - Lay summary - Until the year 2015, consistent replication of patient-derived isolates of hepatitis C virus (HCV) in an in vitro model remained a limitation in HCV research. In 2015 a group of authors identified a protein named SEC14L2 that enabled the replication of HCV isolates in cell culture. We performed a large screen encompassing 73 isolates of 4 different HCV genotypes. Additionally, we replaced the natural SEC14L2 with 13 different mutants to test if the protein variation significantly altered its HCV replication enhancing functions. We showed that different genotypes of HCV react differently to the presence of this protein and the variants of the protein mimic the behavior of the wild-type.
DOI:doi:10.1016/j.jhep.2018.11.012
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 ; Verlag: https://doi.org/10.1016/j.jhep.2018.11.012
 Volltext: http://www.sciencedirect.com/science/article/pii/S0168827818325443
 DOI: https://doi.org/10.1016/j.jhep.2018.11.012
Datenträger:Online-Ressource
Sprache:eng
Sach-SW:Hepatitis C virus
 Host factors
 Polymorphisms
 SEC14L2
 Viral and cellular determinants of HCV replication
K10plus-PPN:1662861842
Verknüpfungen:→ Zeitschrift

Permanenter Link auf diesen Titel (bookmarkfähig):  https://katalog.ub.uni-heidelberg.de/titel/68378616   QR-Code
zum Seitenanfang