<> "The repository administrator has not yet configured an RDF license."^^ . <> . . "Characterization of hepatitis delta virus-like agents: \r\nInsights into evolution, replication dynamics, \r\nand host interactions"^^ . "The human hepatitis delta virus (HDV) is a satellite RNA virus that depends on hepatitis B \r\nvirus (HBV) surface proteins (HBsAg) to form infectious virions. For the past 40 years, the \r\nevolutionary history of HDV has remained largely unknown. Recent discoveries have \r\nrevolutionized our knowledge of HDV biology. HDV-like agents were identified in a vast \r\nand heterogeneous group of vertebrates and invertebrates, highlighting that the evolution \r\nof HDV is more complex than previously foreseen and not restricted to humans as primary \r\nhosts. \r\nHere, I focused on the characterization of HDV-like agents recently discovered in the \r\nwoodchuck (Marmota monax), the white-tailed deer (Odocoileus virginianus), the lesser \r\ndog-like bat (Peropteryx macrotis) and several species of duck (Anas gracilis, Anas \r\ncastanea, Anas superciliosa) in terms of replication, viral spreading pathways and cellular \r\npermissiveness. Viral replication was initiated by transfecting constructs encoding 1.1-fold \r\nover-length antigenomic HDV-like agents (DLA) RNA into human and non-human hepatic \r\nand non-hepatic cell lines. A cell-division-mediated viral amplification assay demonstrated \r\nthe capability of the novel HDV-like agents to replicate and propagate not exclusively in \r\nhepatic tissues and without the requirement of envelopment. \r\nTo elucidate whether the non-human HDV-like agents can exploit the envelope \r\nglycoproteins of hepadna- and other viruses to form infectious particles, I co-transfected \r\ncells with the respective expression constructs and plasmids encoding envelope proteins \r\nfrom different viruses. Strikingly, secretion of pseudo-typed virions capable of establishing \r\ninfection in susceptible target cells was observed. \r\nHDV replication activates interferon (IFN) responses via activation and sensing by MDA5 \r\nand LGP2. HDV-induced IFNs and exogenous IFN-α and -γ profoundly suppressed cell \r\ndivision-mediated HDV spread (CDMS) but had only a minor effect on already ongoing HDV replication in resting cells. The discovery of HDV-like agents provides the chance to \r\ninvestigate the interplay between HDV and IFN response from an evolutionary \r\nperspective. However, appropriate cell culture models to investigate replication, host \r\nfactor dependence and modes of spreading, are lacking. \r\nIn my study, I established a robust infection system for the HDV-like agents found in \r\nwoodchuck (WoDV) and deer (DeDV), overcoming the challenge that they do not express \r\na farnesylated large delta antigen (L-HDAg) and cannot be packaged by HBsAg. After \r\nverifying that these agents, as HDV, can propagate efficiently via CDMS, I packaged their \r\ngenomes with HBsAg by trans-complementation of the HDV L-HDAg. The supernatant \r\nwas used to infect HepaRGNTCP non-targeted control (NT) and HepaRGNTCP MDA5 and/or \r\nLGP2 knock-out (KO) cells always in comparison with HDV. As expected, the HDV \r\nreplication led to IFN activation in HepaRGNTCPNT but not MDA5/LGP2 KO cells. \r\nAccordingly, restriction of CDMS in HepaRGNTCP NT was observed. In contrast, infection \r\nwith WoDV and DeDV induced minor IFN response in HepaRGNTCPNT cells, and the CDMS \r\nof these agents remained efficient independently of MDA5/LGP2 expression. Furthermore,\r\nthe CDMS of WoDV and DeDV was not significantly affected by exogenous IFN treatment. \r\nTherefore, both agents not only lack a strong IFN activation but also display resistance to \r\nIFN treatment. \r\nMy doctoral thesis on the replication, assembly, transmission, and host tropism of novel \r\nHDV-like agents provides insights into the molecular biology, evolution, and virus-host \r\ninteraction of this unique group of agents."^^ . "2024" . . . . . . . "Gnimah Eva"^^ . "Gnouamozi"^^ . "Gnimah Eva Gnouamozi"^^ . . . . . . "Characterization of hepatitis delta virus-like agents: \r\nInsights into evolution, replication dynamics, \r\nand host interactions (PDF)"^^ . . . "Dissertation Gnouamozi 2023hq.pdf"^^ . . . "Characterization of hepatitis delta virus-like agents: \r\nInsights into evolution, replication dynamics, \r\nand host interactions (Other)"^^ . . . . . . "indexcodes.txt"^^ . . . "Characterization of hepatitis delta virus-like agents: \r\nInsights into evolution, replication dynamics, \r\nand host interactions (Other)"^^ . . . . . . "lightbox.jpg"^^ . . . "Characterization of hepatitis delta virus-like agents: \r\nInsights into evolution, replication dynamics, \r\nand host interactions (Other)"^^ . . . . . . "preview.jpg"^^ . . . "Characterization of hepatitis delta virus-like agents: \r\nInsights into evolution, replication dynamics, \r\nand host interactions (Other)"^^ . . . . . . "medium.jpg"^^ . . . "Characterization of hepatitis delta virus-like agents: \r\nInsights into evolution, replication dynamics, \r\nand host interactions (Other)"^^ . . . . . . "small.jpg"^^ . . "HTML Summary of #34852 \n\nCharacterization of hepatitis delta virus-like agents: \nInsights into evolution, replication dynamics, \nand host interactions\n\n" . "text/html" . . . "570 Biowissenschaften, Biologie"@de . "570 Life sciences"@en . .