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Kyle Jung MMED Thesis Final.pdf (4.79 MB)

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Understanding Viral Infection and Lifecycle with Single Cell Transcriptomics

Jung, Kyle Lawrence
http://orcid.org/0000-0002-6694-4333
http://rave.ohiolink.edu/etdc/view?acc_num=case1712324877500664

Abstract Details

2024, Doctor of Philosophy, Case Western Reserve University, Molecular Medicine.
Understanding the viral infection and lifecycle of Severe Fever with Thrombocytopenia Syndrome Virus (SFTSV) and Kaposi’s Sarcoma-Associated Herpesvirus (KSHV) is important in improving disease outcomes and reducing viral prevalence. In our SFTSV study, we discovered specific cytokine profiles associated with the severity of clinical symptoms. We used single cell RNA sequencing (scRNAseq) on patient blood samples to identify a unique expansion of the B cell population in SFTSV-induced fatal cases which indicated that plasma B cells are a primary reservoir of SFSTV replication. These findings present a potential method of reducing the severity of SFTSV infection, especially in aged patients who are more susceptible to adverse outcomes. In our KSHV study, we developed a novel oral 3D infection model and demonstrated that KSHV can only infect exposed basal epithelial cells in the oral epithelia. We used scRNAseq to show that keratinocyte differentiation and cell death pathways were affected by KSHV infection, suggesting that epithelial differentiation could contribute to KSHV reactivation through changes in epigenetic regulation. In addition, we found a unique population of infected cells with limited early lytic gene expression and a unique gene expression profile, which we termed latent-2 cells. These findings demonstrate that our in vitro 3D epithelial ALI culture model should be a valuable tool to further understand oral KSHV infection for the development of future anti-viral therapeutics to block KSHV transmission.
Jae Jung (Advisor)
Feixiong Cheng (Committee Chair)
Weiqiang Chen (Committee Member)
Christine O'Connor (Committee Member)
Frank Esper (Committee Member)
161 p.
Bioinformatics; Biology; Molecular Biology; Virology
virus; viral infection; Severe Fever with Thrombocytopenia Syndrome Virus; Kaposi’s Sarcoma-Associated Herpesvirus; single cell RNA sequencing; air-liquid interface; epithelial differentation; viral reactivation

Recommended Citations

Citations

  • Jung, K. L. (2024). Understanding Viral Infection and Lifecycle with Single Cell Transcriptomics [Doctoral dissertation, Case Western Reserve University]. OhioLINK Electronic Theses and Dissertations Center. http://rave.ohiolink.edu/etdc/view?acc_num=case1712324877500664

    APA Style (7th edition)

  • Jung, Kyle. Understanding Viral Infection and Lifecycle with Single Cell Transcriptomics. 2024. Case Western Reserve University, Doctoral dissertation. OhioLINK Electronic Theses and Dissertations Center, http://rave.ohiolink.edu/etdc/view?acc_num=case1712324877500664.

    MLA Style (8th edition)

  • Jung, Kyle. "Understanding Viral Infection and Lifecycle with Single Cell Transcriptomics." Doctoral dissertation, Case Western Reserve University, 2024. http://rave.ohiolink.edu/etdc/view?acc_num=case1712324877500664

    Chicago Manual of Style (17th edition)

case1712324877500664
83
© 2024, all rights reserved.
This open access ETD is published by Case Western Reserve University School of Graduate Studies and OhioLINK.