CD81 is a restriction factor of EBOV trVLP and is downregulated by EBOV GP and VP40

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dc.contributor.advisor Schindler, Michael (Prof. Dr.) Hu, Dan 2024-03-20T14:09:36Z 2024-03-20T14:09:36Z 2026-03-01
dc.identifier.uri de_DE
dc.description.abstract EBOV, a highly pathogenic filovirus, causes Ebola virus disease to humans with high case fatalities. A broad range of cell types are susceptible for EBOV infection. EBOV entry into host cells is mediated by the viral surface glycoprotein GP, which is also known to play roles in immune evasion by modulating cell surface receptors. Following a flow cytometry-based screen to comprehensively identify EBOV GP modulated surface receptors, this thesis confirmed the downregulations of three tetraspanins, CD81, CD63 and CD9. The downregulations could also be observed in authentic EBOV infection. Moreover, GP of other filoviruses, SUDV, RESTV, TAFV and MARV, can downregulate these tetraspanins as well. The tetraspanins are known to interact with other host proteins and form the tetraspanin enriched microdomains involved in multiple signaling pathways and cellular processes. The functional relevance of the tetraspanins in the EBOV life cycle was characterized by using the EBOV trVLP assay and tetraspanin KO cells. KO of CD81, but not CD63 and CD9, enhanced EBOV minigenome replication and transcription as well as NP oligomerization, which plays an essential role in the formation of EBOV inclusion body, the EBOV replication complex. Conversely, restoration of CD81 expression in CD81 KO cells suppressed EBOV minigenome encoded proteins expression. Moreover, KO of CD81 increased EBOV GP mediated entry and seems to enhance macropinocytosis, the major internalization pathway of EBOV. CD81 was shown to be downregulated by both GP and VP40 of EBOV, which involves lysosomal and proteasomal protein degradation. Notably, a CD81 antibody, 5A6, showed inhibitory effects on EBOV trVLP infection. In summary, EBOV downregulates tetraspanin CD81, as a novel immune evasion mechanism, to create a replication friendly environment. With further investigations of authentic EBOV infection of its primary target cells, CD81 antibody 5A6 might be used as an antiviral treatment. en
dc.description.abstract Die Dissertation ist gesperrt bis zum 1. März 2026 ! de_DE
dc.language.iso en de_DE
dc.publisher Universität Tübingen de_DE
dc.rights ubt-podno de_DE
dc.rights.uri de_DE
dc.rights.uri en
dc.subject.classification Viren de_DE
dc.subject.ddc 570 de_DE
dc.subject.other EBOV en
dc.subject.other CD81 en
dc.subject.other trVLP en
dc.subject.other tetraspanin en
dc.title CD81 is a restriction factor of EBOV trVLP and is downregulated by EBOV GP and VP40 en
dc.type PhDThesis de_DE
dcterms.dateAccepted 2024-02-19
utue.publikation.fachbereich Medizin de_DE
utue.publikation.fakultaet 4 Medizinische Fakultät de_DE
utue.publikation.noppn yes de_DE


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