Masters Theses

Date of Award

8-2016

Degree Type

Thesis

Degree Name

Master of Science

Major

Microbiology

Major Professor

Tim E. Sparer

Committee Members

Sarah L. Lebeis, Barry T. Rouse

Abstract

Human cytomegalovirus (HCMV) causes morbidity and mortality in congenitally infected newborns, transplant recipients, and AIDS patients. Currently, there is no approved CMV vaccine to address these issues. In an effort to develop an alternative treatment to CMV we tested our hypothesis that heparan sulfate binding D-peptides would be effective against multiple HCMV strains in vitro and it would be effective in vivo against murine CMV (MCMV) (Chapter 1). We show that the D-peptide is able to reduce CMV infection in vitro and in vivo. Another approach to combating CMV infections is to neutralize pathogenic factors that contribute to CMV spread and/or pathogenesis. HCMV contains genes with homology to human immune modulators. These genes have been implicated in establishing lifelong HCMV latency. One of these factors is an HCMV expressed viral chemokine (vCXCL-1). CXCL-1 binds to chemokine receptors expressed on host immune cells. In order to understand how vCXCL-1 is involved in CMV pathogenesis we used recombinant MCMV overexpressing chimpanzee CMV vCXCL-1 (vCXCL-1CCMV) and murine CXCL-1 (KC). We hypothesized that CMV encodes vCXCL-1 to aid in viral dissemination (Chapter 2). In contrast we found that over expression of CXC chemokines recruits innate immune cells to the site of infection and primary dissemination organs leading to a dissemination blockade. vCXCL-1 is encoded by the HCMV UL146 gene, which has shown variation among clinical isolates. This variation may attribute contribute to varying clinical outcomes of HCMV infections. We hypothesize that variation in vCXCL-1 leads to differential activation of neutrophils (Chapter 3). Throughout this thesis we have explored how the virus spreads, causes disease and a potential peptide that could be used to prevent the initial CMV infection.

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