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Zika Virus Infection Modulates Expression of Regulatory Complement Factors in SH-SY5Y Cells

Yeung, Jason (2020) Zika Virus Infection Modulates Expression of Regulatory Complement Factors in SH-SY5Y Cells. Master's Thesis, University of Pittsburgh. (Unpublished)

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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.


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Details

Item Type: University of Pittsburgh ETD
Status: Unpublished
Creators/Authors:
CreatorsEmailPitt UsernameORCID
Yeung, Jasonjasonyeung012@gmail.comJAY71
ETD Committee:
TitleMemberEmail AddressPitt UsernameORCID
Committee ChairMarques, Ernesto
Committee MemberAyyavoo, Velpandi
Committee MemberD'Aiuto, Leonardo
Date: 30 July 2020
Date Type: Publication
Defense Date: 10 April 2020
Approval Date: 30 July 2020
Submission Date: 15 May 2020
Access Restriction: No restriction; Release the ETD for access worldwide immediately.
Number of Pages: 81
Institution: University of Pittsburgh
Schools and Programs: Graduate School of Public Health > Infectious Diseases and Microbiology
Degree: MS - Master of Science
Thesis Type: Master's Thesis
Refereed: Yes
Uncontrolled Keywords: Zika Virus, Flavivirus, Complement System, Brain, Neurovirology
Date Deposited: 30 Jul 2020 21:16
Last Modified: 30 Jul 2020 21:16
URI: http://d-scholarship.pitt.edu/id/eprint/39036

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