INVESTIGATING THE ROLES OF HERPES SIMPLEX VIRUS TYPE 2 PROTEINS UL21 AND US3 IN REGULATION OF THE NUCLEAR EGRESS COMPLEX
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Authors
Muradov, Jamil
Date
Type
thesis
Language
eng
Keyword
Herpesvirus , Nuclear Egress , Inner Nuclear Membrane , Us3 , UL31 , UL34 , UL21 , Tegument , Alphaherpesvirinae , Herpes Simplex Virus , HSV-2 , Primary Enveloped Virion , Viral kinase , Phos-tag western blotting
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Abstract
Herpes Simplex Virus 2 (HSV-2) nuclear egress is mediated by viral nuclear egress complex (NEC) proteins, pUL31 and pUL34, found at the inner nuclear membrane of infected cells (INM). Nuclear egress requires successful primary envelopment of a capsid at the INM, budding of the resulting capsid-containing vesicle into the perinuclear space (PNS), de-envelopment of the perinuclear virion at the outer nuclear membrane and release of the capsid into the cytoplasm. In this work, we demonstrate that HSV-2 pUL31 and pUL34 are phosphorylated by a viral protein kinase, called pUs3, which serves to prevent excessive INM deformation and accumulation of the primary enveloped virions (PEVs) in PNS after successful primary envelopment of capsids. It was found that a tegument protein, pUL21, modulates pUs3 dependent pUL31 and pUL34 phosphorylation. We also determined that in UL21-knockout infected cells, pUs3 is differentially modified, and this modification is likely an autophosphorylation. Higher levels of pUs3 phosphorylation were shown to result in augmentation of pUs3/PKA substrate phosphorylation levels, including pUL31 and pUL34. Excessive phosphorylation of the NEC components caused their aberrant distribution at the INM, extravagation of the nuclear envelope and failure of the capsids to undergo primary envelopment at the INM. We, therefore, postulate that that Us3 and UL21 deletions cause different types of the nuclear envelope defects in infected cells and that pUL21 acts upstream of pUs3 as a modulator of its kinase activity. This regulation mechanism was shown to be specific to HSV-2 and does not function in HSV-1 infected cells.
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ProQuest PhD and Master's Theses International Dissemination Agreement
Intellectual Property Guidelines at Queen's University
Copying and Preserving Your Thesis
This publication is made available by the authority of the copyright owner solely for the purpose of private study and research and may not be copied or reproduced except as permitted by the copyright laws without written authority from the copyright owner.
CC0 1.0 Universal