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Impact of Zika virus on human dendritic cells

Good, Matthew (2018) Impact of Zika virus on human dendritic cells. Master's Thesis, University of Pittsburgh. (Unpublished)

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Zika virus (ZIKV) is a mosquito-borne flavivirus, transmitted to humans by Aedes aegypti and Aedes albopictus mosquitos, and has also more recently been shown to transmit from human-to-human sexually and vertically from mother to fetus. ZIKV infection, typically causing mild clinical symptoms, has been linked to a range of neurological complications including microcephaly in fetuses and Guillain-Barré syndrome in adults. ZIKV’s recent emergence poses a public health emergency, and new pathological information is required for developing effective interventions to ameliorate the burden of disease. The dendritic cell (DC), the key innate immune responder that ultimately drives anti-viral adaptive immunity, has known interactions with ZIKV. However, the nature of this interaction, and the DCs role in ZIKV pathology needs further elucidation. Here we hypothesize ZIKV can infect and modify the phenotype and function of dendritic cells, which influences the nature of their subsequent interplay with pre-existing ZIKV antigen responsive memory T cells. We found that ZIKV can indeed infect both immature and mature DCs, and that DCs can transfer infection to bystander cells. We also found that exposure of DCs to ZIKV alters their function, maturation status, and survival. Interestingly, we note that the capacity of ZIKV to infect DCs is greatly influenced by the environmental signals received by DCs during their maturation process, and that type-1 polarized DC are inherently more resistant than type-2 matured DC. Importantly, when activated by the CD4+ T cell helper signal CD40L, ZIKV infected DC proved to be more resistant to ZIKV-induced cell death. And finally, on the background of dengue virus immunity, we found that dengue antigen specific memory T cells cross-react with ZIKV antigen presented by DC, leading to enhanced DC activation rather than elimination. In terms of public health significance, these findings may contribute to our understanding of basic ZIKV and DC interactions, and may help to provide a better understanding of ZIKV pathogenesis leading towards the development of effective interventions to protect and treat those who may become exposed to ZIKV.


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Item Type: University of Pittsburgh ETD
Status: Unpublished
CreatorsEmailPitt UsernameORCID
Good, Matthewmgg23@pitt.edumgg23
ETD Committee:
TitleMemberEmail AddressPitt UsernameORCID
Committee ChairMailliard, Robert
Committee MemberPiazza, Paolo
Committee MemberAdibi, Jennifer
Date: 5 April 2018
Date Type: Submission
Defense Date: 20 April 2018
Approval Date: 28 June 2018
Submission Date: 26 April 2018
Access Restriction: 2 year -- Restrict access to University of Pittsburgh for a period of 2 years.
Number of Pages: 69
Institution: University of Pittsburgh
Schools and Programs: School of Public Health > Infectious Diseases and Microbiology
Degree: MS - Master of Science
Thesis Type: Master's Thesis
Refereed: No
Uncontrolled Keywords: zika, dc
Date Deposited: 28 Jun 2018 20:06
Last Modified: 01 May 2020 05:15


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