Investigating the Role of UL16 in the Nuclear Egress of Herpesvirus Capsids
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Authors
Lubinsky, Ali
Date
Type
thesis
Language
eng
Keyword
herpesvirus , UL16 , nuclear egress , BioID
Alternative Title
Abstract
Herpes simplex virus type 2 (HSV-2) is a highly prevalent human pathogen that remains the primary cause of ulcerative genital lesions and poses a significant impact on human health. Infectious HSV-2 virions contain a proteinaceous layer that is located between the capsid and envelope, known as the tegument, the contents of which contribute to multiple aspects of the viral life cycle, including virion assembly and egress. The HSV-2 UL16 gene encodes a highly conserved tegument protein, called pUL16, whose function is poorly understood. Previous reports from our laboratory have indicated that, in the absence of pUL16, newly assembled capsids are not recruited to the inner nuclear membrane (INM) efficiently during an early stage of virion morphogenesis, called nuclear egress. Therefore, we hypothesized that pUL16 promotes nuclear egress by facilitating the recruitment of capsids to the INM. In this study, we conducted proximity-dependent biotin identification (BioID) experiments to identify cellular and viral proteins that are in proximity to pUL16 during virus infection, including the process of nuclear egress. To do so, we constructed a recombinant HSV-2 strain, expressing pUL16 fused to miniTurbo (mT), a biotin ligase, purified proteins biotinylated by the pUL16mT fusion protein, and identified these pUL16-proximal proteins by mass spectrometry. We identified 569 unique proteins, 102 of which were regarded as strong candidates for further analysis. Several virion structural components that are known to interact with pUL16 were identified, along with various proteins that provide insight into functions of pUL16, in addition to those related to nuclear egress. Additionally, certain host antiviral proteins, such as gamma-interferon-inducible protein 16 (IFI16) and zinc finger CCCH-type antiviral protein 1 (ZAP), were identified in proximity to pUL16, suggesting that pUL16 may modulate host antiviral responses. Lastly, we identified several proteins that contribute to nucleocytoplasmic transport as well as those that are components of the nuclear envelope, providing insight into the role of pUL16 in nuclear egress. Collectively, this study identifies several candidate pUL16-proximal proteins that will be further investigated in future studies, in order to provide greater insight into the specific role(s) of pUL16 during HSV-2 infection.
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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.