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Viral Encephalitis: phenotyping leukocyte infiltration into the central nervous system as a result of Rift Valley Fever Virus infection

Albe, Joseph R (2017) Viral Encephalitis: phenotyping leukocyte infiltration into the central nervous system as a result of Rift Valley Fever Virus infection. Master's Thesis, University of Pittsburgh. (Unpublished)

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Abstract

Rift Valley Fever Virus (RVFV) is a vector-borne infection endemic to the Horne of Africa; However, outbreaks in the Arabian Peninsula in 2001 demonstrate its expanding range. Humans can develop encephalitis as a result of RVFV infection. Our lab uses an immunocompetent Lewis rat model to study neuropathogenesis of RVFV. With this model, Lewis rats uniformly develop lethal encephalitis within 7 – 8 days after aerosol exposure. In contrast, Lewis rats infected subcutaneously do not develop apparent disease except at very high doses. The public health significance of RVFV is that it has the potential to natural spread throughout the world and it could be used as a potential bioweapon. The goal of this study is to characterize the phenotypes, timing, and extent of immune cell infiltrate into the CNS of RVFV-infected Lewis rats. Lewis rats were infected with RVFV ZH501 by aerosol or subcutaneous routes, and subsequently serially-sacrificed between 1 and 7 days post infection. Rat immune cells were isolated from brains via percoll gradients, stained with the appropriate antibodies, run on a BD LSRII flow cytometer, and analyzed with FlowJo 7.6.5.
In aerosol-infected rats, the leukocyte infiltrate 5 days post infection and later consisted of primarily neutrophils, corresponding to the clinical window. Despite no apparent disease, rats infected subcutaneously had detectable infiltrate primarily consisting of phenotypic CD4+ T cells. These findings suggest that aerosol-infected rats mainly exhibit innate leukocyte infiltration to the brain while subcutaneous have limited leukocyte infiltration and display a stronger adaptive immune response. The relative contributions of viral cytopathology versus immunopathology remain to be determined, but this study represent the first attempt to characterize the leukocytic component of RVFV neurological disease.


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Details

Item Type: University of Pittsburgh ETD
Status: Unpublished
Creators/Authors:
CreatorsEmailPitt UsernameORCID
Albe, Joseph Rjra48@pitt.edujra48
ETD Committee:
TitleMemberEmail AddressPitt UsernameORCID
Committee ChairHartman, Amyhartman2@pitt.edu
Committee MemberReed, Douglasdsreed@pitt.edu
Committee MemberMailliard, Robbierbm19@pitt.edu
Centers: Other Centers, Institutes, Offices, or Units > Center for Vaccine Research
Date: 29 June 2017
Date Type: Publication
Defense Date: 13 April 2017
Approval Date: 29 June 2017
Submission Date: 25 April 2017
Access Restriction: No restriction; Release the ETD for access worldwide immediately.
Number of Pages: 74
Institution: University of Pittsburgh
Schools and Programs: Graduate School of Public Health > Infectious Diseases and Microbiology
Degree: MPH - Master of Public Health
Thesis Type: Master's Thesis
Refereed: No
Uncontrolled Keywords: Rift Valley Fever Virus
Date Deposited: 29 Jun 2017 22:30
Last Modified: 01 May 2020 05:15
URI: http://d-scholarship.pitt.edu/id/eprint/31586

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