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Identifier |
000409441 |
Title |
The role of Rho family GTPases in Human Cytomegalovirus infection (Human Cytomegalovirus, HCMV) |
Alternative Title |
Ο ρόλος των πρωτεϊνών Rho GTPases κατά τη διάρκεια της μόλυνσης από τον ανθρώπινο κυτταρομεγαλοϊό. |
Author
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Τσέλιου, Μελπομένη
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Thesis advisor
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Σουρβίνος, Γεώργιος
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Select a value
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Στουρνάρας, Χρήστος
Τσατσάνης, Χρήστος
Χαμηλός, Γιώργος
Γουλιέλμος, Γιώργος
Τζαρδή, Μ.
Ζαφειρόπουλος, Α.
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Abstract |
Human cytomegalovirus (HCMV) is one of the eight human herpesviruses with worldwide distribution and a high clinical importance. It is a beta herpes virus with double stranded DNA and establishes a lifelong latent infection after a primary infection. Rho GTPases are crucial regulators of the actin cytoskeleton and play a role in controlling membrane trafficking and cell signaling. The actin cytoskeleton of the host cell and actin regulating Rho GTPase signaling pathways are involved in several of the interactions of human cells with viral components. This has provided scientific data so as to investigate further on the Human Cytomegalovirus (HCMV). So far, there is short evidence on the role of Rho GTPases during HCMV infection.
In the present thesis, we studied the mechanism that controls infection by HCMV investigating two directions; the effect of RhoA and the role of RhoA depletion during the course of infection and the effect of silencing RhoA, RhoB or RhoC in HCMV infected glioblastoma cells.
The first part of this thesis focused in the analysis of the effect of RhoA silencing during the various early and late stages of HCMV infection to establish whether RhoA and RhoA downstream effectors are directly involved in promoting productive HCMV infection. Therefore it was of high priority to investigate the effect of RhoA and the role of RhoA knockdown at the early stages of infection that occur immediately after viral uptake into the host cell as well at the later stages during viral egress. Collectively, it was demonstrated that RhoA knockdown provides benefit to early and late stages of HCMV infection by the inhibition of the RhoA and ROCK1 pathway. At the second part of the study, we analyzed modifications in the organization of the actin cytoskeleton that are regulated by RhoA, RhoB and RhoC GTPases and affect cell motility and migration in HCMV infected cancer cells in order to explore properties of HCMV and its capability to modulate the tumor microenvironment. Taken together these data, we suggest a possible direct or indirect involvement of Rho small GTPases during HCMV infection with potential role in cell morphology, proliferation and migration of human glioblastoma cells.
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Language |
English |
Subject |
Cell migration |
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Glioblastoma cells |
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Κυτταρική μετανάστευση |
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Κυτταρικός πολλαπλασιασμός |
Issue date |
2017-07-26 |
Collection
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School/Department--School of Medicine--Department of Medicine--Doctoral theses
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Type of Work--Doctoral theses
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Views |
663 |