Document Type

Honors Thesis

Publication Date

5-2012

Abstract

Upon viral infection, the host’s immune system can induce the antiviral state to protect from further infection. In this antiviral state, RNA synthesis and protein synthesis are downregulated, and viral replication is inhibited (Kawai and Akira, 2006). Two of the key pathways critical to establishing the antiviral state include the Toll-like receptor (TLR) and the interferon (IFN) receptor (IFNR) pathways (Kawai and Akira, 2006). The TLR pathway is critical to recognizing viral components, while the IFNR pathway is vital to activating genes necessary for inducing the antiviral state. As the host evolves to combat viral infections, viruses have also evolved to circumvent such host antiviral immune response. One viral evasion mechanism is via disruption of cell membrane domains known as caveolae. Caveolae membrane domains are critical to maintaining a platform from which molecules can signal and have been implicated in a variety of disease processes, including breast and prostate cancer, type II diabetes, and atherosclerosis (Cohen et al., 2004).

Previous studies show that viral infection leads to a downregulation in caveolin transcripts and the dispersal of IFNR clusters (Gabor et al., Submitted). As a result, the host’s antiviral immune response is dampened. In the present study, I suggest a role for caveolae in the TLR9 signaling pathway. Through Fluorescence Photoactivation Localization Microscopy (FPALM) imaging, I observe spatial overlap, or colocalization, of TLR9 and caveolin molecules. When caveolin is depleted, TLR9 signaling, upon exposure to unmethylated CpG DNA, is dampened. Understanding the mechanisms by which a pathogen may evade the host’s immune system will provide further insights into new and effective treatments, such as IFN and TLR antiviral therapies.

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Microbiology Commons

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