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Ex Vivo Salivary Gland Culture as a Novel System to Evaluate HCMV Infection

Morrison, Kristen M.
http://rave.ohiolink.edu/etdc/view?acc_num=ucin1470044093

Abstract Details

2016, MS, University of Cincinnati, Medicine: Molecular Genetics, Biochemistry, and Microbiology.
Human Cytomegalovirus (HCMV), also known as human herpesvirus 5 (HHV5), and the related rodent and non-human primate cytomegaloviruses (MCMV, RCMV and rhCMV), encode G-protein coupled receptors (GPCRs) that appear to play important roles during CMV infection including viral dissemination, cellular migration, and viral latency. The rodent viruses encode two GPCRs, while the human and non-human primate viruses encode four GPCRs. Although divergent in primary amino acid sequence, these viral encoded GPCRs share highest homology with members of the chemokine receptor (CKR) subfamily including CCR1 and CCR5. The HCMV encoded GPCR, US28 is particularly interesting due to its ability to exploit multiple G-protein dependent and G-protein independent pathways. One signaling pathway that has been shown to be US28-dependent but independent of ligand activation is the Gaq/11 mediated phospholipase Cß (PLCß) pathway. PLCß hydrolyzes phosphatidylinositol 4,5-bisphosphate into diacylglycerol (DAG) and inositol 1,4,5-trisphosphate (IP3). The production of DAG and IP3 promotes the downstream activation of protein kinase C (PKC) and the release of Ca2+ from intracellular stores, respectively. Several studies have been conducted which indicate important roles for US28 during viral infection, however, the full extent of US28 signaling pathways and how these signaling pathways contribute to the US28 function during infection has yet to be uncovered. Furthermore, the predominant models used to study CMV infection and viral GPCR signaling are that of mice and immortalized human cell lines. Studies in mice have revealed essential roles for the MCMV GPCRs in facilitating viral replication in salivary tissues in vivo which is important for horizontal transmission, however similar studies with the HCMV GPCRs have not been carried out due to limitations in tissue and cellular systems. With recent advances in various tissue engineering strategies, it has now become possible to culture ex vivo human salivary gland cells and thus our work aims to develop a novel system in which primary human salivary gland cells are used to model HCMV infection and explore mechanisms governing viral replication and spread within this tissue. The development of such a system will facilitate future studies aimed at exploring a potential role for US28 and its signaling activity in regulating HCMV replication and spread in salivary tissue similar to that of its rodent viral counterpart, M33.
William Miller, Ph.D. (Committee Chair)
Edmund Choi, Ph.D. (Committee Member)
Rhett Kovall, Ph.D. (Committee Member)
75 p.
Molecular Biology
salivary gland; cytomegalovirus; HCMV; US28; ex vivo; culture model

Recommended Citations

Citations

  • Morrison, K. M. (2016). Ex Vivo Salivary Gland Culture as a Novel System to Evaluate HCMV Infection [Master's thesis, University of Cincinnati]. OhioLINK Electronic Theses and Dissertations Center. http://rave.ohiolink.edu/etdc/view?acc_num=ucin1470044093

    APA Style (7th edition)

  • Morrison, Kristen. Ex Vivo Salivary Gland Culture as a Novel System to Evaluate HCMV Infection. 2016. University of Cincinnati, Master's thesis. OhioLINK Electronic Theses and Dissertations Center, http://rave.ohiolink.edu/etdc/view?acc_num=ucin1470044093.

    MLA Style (8th edition)

  • Morrison, Kristen. "Ex Vivo Salivary Gland Culture as a Novel System to Evaluate HCMV Infection." Master's thesis, University of Cincinnati, 2016. http://rave.ohiolink.edu/etdc/view?acc_num=ucin1470044093

    Chicago Manual of Style (17th edition)

ucin1470044093
352
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This open access ETD is published by University of Cincinnati and OhioLINK.