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| Identifier |
000401068 |
| Title |
Study of the cellular signaling pathways during latent infection and reactivation by HSV-1 (Herpes Simplex Virus type 1) |
| Alternative Title |
Μελέτη των κυτταρικών, σηματοδοτικών μονοπατιών κατά τη διάρκεια λανθάνουσας μόλυνσης και επανενεργοποίησης από τον ιό του απλού έρπητα τύπου 1 (Herpes Simplex Virus type I, HSV-1) |
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Author
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Βλαχάβα, Βιργινία-Μαρία
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Thesis advisor
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Σουρβίνος, Γεώργιος
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Reviewer
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Ηλιόπουλος, Αριστείδης
Πανουτσακοπούλου, Βίλη
Καμπράνης, Σ
Καρδάσης, Δημήτριος
Ππαδάκη, Ελένη
Τσατσάνης, Χρήστος
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| Abstract |
HSV-1 is a DNA virus of the herpesviruses family (Herpesviridae) and specifically
belongs to the Alpha subfamily (Alphaherpesvirinae). It is a neurotropic virus that
alternates from a lytic cycle in epithelial cells to a latent cycle in neurons. Its lytic cycle
takes place in three phases, the immediate early (IE), the early (E) and the late (L).
In the present thesis, we studied the mechanisms that govern infection by Herpes
Simplex virus type-1 investigating two directions; the effect of CD40L on the outcome
of infection and the methylation profile of host genes during the course of infection.
In the first part, the effect of CD40L on HSV-1 infection was studied and it was found
that CD40L directly inhibits infection by HSV-1 following entry of the virus in the host
cell. Different stages of viral infection were analyzed as well as antiviral mechanisms
with a particular emphasis on autophagy. Collectively, it was demonstrated that HSV-
1 is directly inhibited by the activation of the CD40L pathway by a mechanism that is
PI3K-dependent and autophagy-independent.
At the second part of the study, the methylation profile of the host cell genome was
analyzed during lytic and latent infection by HSV-1 with particular interest on the
enzymes associated to epigenetic phenomena. PCR-array analysis showed that there
is a great variation in the methylation profile during the immediate early (IE) and early
(E) phase of infection while in the late (L) phase of infection and in latently infected
cells the methylation profile remains stable, however, different from the steady state
methylation of the host. Several histone deacetylase genes were identified as targets
for alterations in DNA methylation and an effort was made to correlate the changes in
DNA methylation to gene expression and their impact on the progeny virus.
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| Language |
English |
| Subject |
Autophagy |
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CD40 ligand |
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Epigenetics |
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LSD1 |
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PIK3K |
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VP16 |
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Αυτοφαγία |
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Επιγενετική |
| Issue date |
2015-07-14 |
| 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 |
257 |
Study of the cellular signaling pathways during latent infection and reactivation by HSV-1 (Herpes Simplex Virus type 1)
