eprintid: 39036
rev_number: 11
userid: 9609
dir: disk0/00/03/90/36
datestamp: 2020-07-30 21:16:14
lastmod: 2020-07-30 21:16:14
status_changed: 2020-07-30 21:16:14
type: thesis_degree
metadata_visibility: show
contact_email: jasonyeung012@gmail.com
item_issues_id: duplicate_title_38468
item_issues_type: duplicate_title
item_issues_description: Duplicate title to 


    <span class="person_name">Yeung, Jason</span>
  



<a href="http://d-scholarship.pitt.edu/cgi/users/home?screen=EPrint::View&amp;eprintid=38468"><xhtml:em xmlns:xhtml="http://www.w3.org/1999/xhtml">Zika Virus Infection Modulates Expression of Regulatory Complement Factors in SH-SY5Y Cells.</xhtml:em></a>


    Master's Thesis, University of Pittsburgh.
  


   (Unpublished)
item_issues_timestamp: 2020-05-16 06:02:25
item_issues_status: autoresolved
item_issues_count: 0
eprint_status: archive
creators_name: Yeung, Jason
creators_email: jasonyeung012@gmail.com
creators_id: JAY71
title: Zika Virus Infection Modulates Expression of Regulatory Complement Factors in SH-SY5Y Cells
ispublished: unpub
divisions: sch_gsph_infectiousdiseasesmicrobiology
full_text_status: public
keywords: Zika Virus, Flavivirus, Complement System, Brain, Neurovirology
abstract: Viruses that use the blood as a route of systemic spread frequently encode proteins allowing evasion of the complement system. Although complement neutralizes pathogens in the blood, the complement system has non-immune functions in the central nervous system (CNS) and mediates non-viral neuropathologies when triggered by damaging stimuli. 
As viruses capable of both hematogenous spread and neuroinvasion, flaviviruses such as Zika virus (ZIKV) are a significant public health issue as the most common cause of arboviral disease. Outside of the brain, flaviviruses can modulate levels of complement proteins and surface bound complement regulators. We hypothesized that similar alterations occur in CNS cells, contributing to viral neuropathology. 
In this study, we establish the relevance of viral complement modulation in infection of CNS cells. Using various CNS culture systems, endogenous expression of complement proteins and complement-related surface markers was investigated.  In a co-culture system of cell lines SH-SY5Y (neuroblastoma) and HMC3 (microglia), endogenous complement protein production was confirmed in absence of Zika infection and stimulation. Furthermore, Zika infection modulated expression of surface bound inhibitors CD46 and CD55. Compared to mock, CD46 was upregulated in both infected and non-infected, bystander cells with stronger expression in infected cells. CD55 was equally downregulated in infected and bystander cells. Finally, affinity between ZIKV non-structural protein 1 (NS1) and complement proteins was demonstrated. 
These results support previous studies implicating complement modulation as a source of pathology in neuro-invasive flavivirus infection, providing insight on the precise biochemical changes behind this process.
date: 2020-07-30
date_type: published
pages: 81
institution: University of Pittsburgh
refereed: TRUE
etdcommittee_type: committee_chair
etdcommittee_type: committee_member
etdcommittee_type: committee_member
etdcommittee_name: Marques, Ernesto
etdcommittee_name: Ayyavoo, Velpandi
etdcommittee_name: D'Aiuto, Leonardo
etd_defense_date: 2020-04-10
etd_approval_date: 2020-07-30
etd_submission_date: 2020-05-15
etd_release_date: 2020-07-30
etd_access_restriction: immediate
etd_patent_pending: FALSE
thesis_type: thesis
degree: MS
citation:   Yeung, Jason  (2020) Zika Virus Infection Modulates Expression of Regulatory Complement Factors in SH-SY5Y Cells.  Master's Thesis, University of Pittsburgh.    (Unpublished)  
document_url: http://d-scholarship-dev.library.pitt.edu/39036/1/Yeung_Jason_MSthesis_4_2020.pdf