Identification of host factors for the replication of the Kaposi’s sarcoma- associated herpesvirus (KSHV) and the related rhesus monkey rhadinovirus (RRV)

Scribano, Stefano

dc.contributor.advisor	Hahn, Alexander Dr.
dc.contributor.author	Scribano, Stefano
dc.date.accessioned	2024-07-23T15:27:59Z
dc.date.available	2024-07-30T00:50:08Z
dc.date.issued	2024-07-23
dc.identifier.uri	http://resolver.sub.uni-goettingen.de/purl?ediss-11858/15386
dc.identifier.uri	http://dx.doi.org/10.53846/goediss-10628
dc.format.extent	88	de
dc.language.iso	eng	de
dc.rights.uri	http://creativecommons.org/licenses/by/4.0/
dc.subject.ddc	570	de
dc.title	Identification of host factors for the replication of the Kaposi’s sarcoma- associated herpesvirus (KSHV) and the related rhesus monkey rhadinovirus (RRV)	de
dc.type	doctoralThesis	de
dc.contributor.referee	Hahn, Alexander Dr.
dc.date.examination	2023-10-02	de
dc.description.abstracteng	Kaposi’s sarcoma-associated herpesvirus (KSHV) is a human tumor virus. It is associated with Kaposi’s sarcoma, primary effusion lymphoma, and multicentric Castleman’s disease. KSHV is known to interact with several different receptors, among them heparan sulfate proteoglycans, Eph family receptors, and integrins. We mutated the closely related rhesus monkey rhadinovirus in the known receptor interaction sites for Eph family and Plexin domain containing proteins and found it to still replicate on certain cells. This lytic virus was then used as a selection agent in a genome-wide CRISPR knockout screen, which identified TIM1 and NRP1 as host dependency factors. NRP1 is also host factor for the related Epstein-Barr virus and was recently reported to promote KSHV infection, which we confirm even if it functions with low efficiency on most cells and became functional only after ablation of the Eph receptor interaction. Further analysis through overexpression demonstrated that Tim-1 and the related Tim-4 are strong mediators of RRV and KSHV infection, in particular in the absence of other receptor interactions and even more pronounced for a KSHV mutant deleted in glycoprotein K8.1. Both Tim-1 and Tim-4 are heavily O-glycosylated phosphatidylserine (PS) receptors. For KSHV in particular, experiments with mutated Tim-1 and comparison to Ebola virus glycoprotein-driven entry indicate that the interaction with Tim-1 occurs through PS-binding by Tim-1 and suggest additional interaction in a PS-independent manner. The mucin-like domain of Tim-1 is required for optimal receptor function. The use of Tim proteins for entry is a novelty for herpesviruses and underscores the unique biology of KSHV and RRV.	de
dc.contributor.coReferee	Pöhlmann, Stefan Prof. Dr.
dc.contributor.thirdReferee	Walter, Lutz Prof. Dr.
dc.contributor.thirdReferee	Winkler, Michael PD Dr.
dc.contributor.thirdReferee	Roos, Christian Dr.
dc.contributor.thirdReferee	Behr, Rüdiger Prof. Dr.
dc.subject.eng	Gammaherpesviruses	de
dc.subject.eng	KSHV	de
dc.subject.eng	RRV	de
dc.subject.eng	T-cell immunoglobulin and mucin domain	de
dc.subject.eng	Tim-1	de
dc.subject.eng	Tim-4	de
dc.identifier.urn	urn:nbn:de:gbv:7-ediss-15386-5
dc.affiliation.institute	Biologische Fakultät für Biologie und Psychologie	de
dc.subject.gokfull	Biologie (PPN619462639)	de
dc.description.embargoed	2024-07-30	de
dc.identifier.ppn	1896581811
dc.identifier.orcid	https://orcid.org/0000-0003-4269-4111	de
dc.notes.confirmationsent	Confirmation sent 2024-07-23T19:45:01	de

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GGNB - Göttinger Graduiertenzentrum für Neurowissenschaften, Biophysik und molekulare Biowissenschaften [1153]
GGNB - Göttingen Graduate Center for Neurosciences, Biophysics and Molecular Biosciences

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