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USING MUTAGENESIS AND STEM CELLS TO UNDERSTAND RETROVIRAL NEUROVIRULENCE

Renszel, Krystal Marie
http://rave.ohiolink.edu/etdc/view?acc_num=kent1254659655

Abstract Details

2009, MS, Kent State University, College of Arts and Sciences / School of Biomedical Sciences.
Certain retroviruses are capable of causing progressive spongiform neurodegeneration which results in paralysis, wasting and death; however, the disease mechanism remains unknown. In this study, we have investigated the role that N-linked glycosylation plays in the pathogenic process by site-directed mutagenesis of a prototypic neruovirulent env from CasBrE, followed by in vitro and in vivo analyses. Mutations were introduced to mimic the precise context in which existing glycosylation sites were located in the related non-neurovirulent (NN) ecotropic Env MuLV, Friend virus clone 57 (Fr57E). Mutations drastically affected in vitro viral replication and spread as well as Env protein processing, leading to classification of glycosylation site mutant viruses into three general phenotypes: wild-type-like, replication-comprised, and viruses with no infectivity, so-called dead viruses. Wild-type-like viruses which progressively approximated Fr57 Env glycosylation were injected intraperitoneally into susceptible IRW mice, resulting in neuropathological changes similar to wild type FrCasE. To circumvent the low viral infectivity with the replication-compromised viruses, virus-expressing neural stem cells were transplanted into the brainstem in order to disseminate virus directly into susceptible brain regions. These transplants resulted in focal spongiform neuropathology, despite significant changes in Env biology. This data suggest that while modification of Env glycosylation sequences can dramatically affect in vitro and in vivo viral function and spread, protein processing, and virion incorporation, these changes do not appear to dramatically impact the ability of Env to precipitate neurodegeneration. These results have broader implications as to what mechanisms might actually be involved in CasBrE Env-induced neurodegeneration.
William Lynch, PhD (Advisor)
Kenneth Rosenthal, PhD (Committee Member)
Jeffrey Wenstrup, PhD (Committee Member)
82 p.
Biomedical Research
retrovirus; neurodegeneration; protein glycosylation

Recommended Citations

Citations

  • Renszel, K. M. (2009). USING MUTAGENESIS AND STEM CELLS TO UNDERSTAND RETROVIRAL NEUROVIRULENCE [Master's thesis, Kent State University]. OhioLINK Electronic Theses and Dissertations Center. http://rave.ohiolink.edu/etdc/view?acc_num=kent1254659655

    APA Style (7th edition)

  • Renszel, Krystal. USING MUTAGENESIS AND STEM CELLS TO UNDERSTAND RETROVIRAL NEUROVIRULENCE. 2009. Kent State University, Master's thesis. OhioLINK Electronic Theses and Dissertations Center, http://rave.ohiolink.edu/etdc/view?acc_num=kent1254659655.

    MLA Style (8th edition)

  • Renszel, Krystal. "USING MUTAGENESIS AND STEM CELLS TO UNDERSTAND RETROVIRAL NEUROVIRULENCE." Master's thesis, Kent State University, 2009. http://rave.ohiolink.edu/etdc/view?acc_num=kent1254659655

    Chicago Manual of Style (17th edition)

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© 2009, all rights reserved.
This open access ETD is published by Kent State University and OhioLINK.