eprintid: 31611
rev_number: 16
userid: 6522
dir: disk0/00/03/16/11
datestamp: 2017-06-29 23:32:26
lastmod: 2020-05-01 05:15:06
status_changed: 2017-06-29 23:32:26
type: thesis_degree
metadata_visibility: show
contact_email: lxsalama@gmail.com
eprint_status: archive
creators_name: Salama, Noah
creators_email: NAS197@pit.edu
creators_id: NAS197
title: Analysis of peripheral immune responses for the development of an encephalitis non-human primate animal model for new world alphaviruses
ispublished: unpub
divisions: sch_gsph_infectiousdiseasesmicrobiology
full_text_status: public
keywords: Viral encephalitis, alphavirus, animal model, immunology, neuroinflammation
abstract: The New World alphaviruses eastern equine encephalitis virus (EEEV), Venezuelan equine encephalitis virus (VEEV), and western equine encephalitis virus (WEEV) are all mosquito-borne pathogens originating in North and South America. All three viruses are capable of causing severe illness in animals and humans, with extreme cases leading to encephalitis. Given the lack of commercially available vaccines or treatments, and previous research into these pathogens as potential bioterrorism weapons, all three are of great significance to public health. The aim of our laboratory was to develop a cynomolgus macaque model to study the unique neuropathology of each virus when delivered via an aerosol route, the most likely delivery route for a biological attack. To assess pathogenesis, peripheral blood mononuclear cells (PBMCs) were isolated from whole blood and analyzed by flow cytometry. Inflammation in the central nervous system (CNS) was also evaluated using a LEGENDplex bead based immunological array. Results indicate a substantial increase in the number of CCR2+ myeloid cells in circulation, a receptor important for homing and migration to infected tissue. In addition, inflammatory cytokines MCP-1 (CCL-2), IP-10, IL-6, and IL-8 were substantially upregulated in the CNS tissues and cerebrospinal fluid (CSF) of lethally infected animals. Collectively, this suggests homing and migration of peripheral immune cells to the CNS, and identifies potential markers for future longitudinal studies of alphavirus disease progression and severity.
date: 2017-06-29
date_type: published
pages: 85
institution: University of Pittsburgh
refereed: TRUE
etdcommittee_type: thesis_advisor
etdcommittee_type: committee_member
etdcommittee_type: committee_member
etdcommittee_type: committee_member
etdcommittee_name: Hartman, Amy
etdcommittee_name: Mailliard, Robbie
etdcommittee_name: Barratt-Boyes, Simon
etdcommittee_name: Klimstra, William
etdcommittee_email: hatman2@pitt.edu
etdcommittee_email: rbm19@pitt.edu
etdcommittee_email: smbb@pitt.edu
etdcommittee_email: klimstra@pitt.edu
etd_defense_date: 2017-04-19
etd_approval_date: 2017-06-29
etd_submission_date: 2017-04-27
etd_release_date: 2017-06-29
etd_access_restriction: 3_year
etd_patent_pending: FALSE
thesis_type: thesis
degree: MS
citation:   Salama, Noah  (2017) Analysis of peripheral immune responses for the development of an encephalitis non-human primate animal model for new world alphaviruses.  Master's Thesis, University of Pittsburgh.    (Unpublished)  
document_url: http://d-scholarship-dev.library.pitt.edu/31611/7/Revised%20Thesis.pdf