Date of Award

Spring 5-16-2015

Degree Type

Thesis

Degree Name

MS Microbiology

Department

Biology

Advisor

Daniel B. Nichols, Ph.D

Committee Member

Tin-Chun Chu, Ph.D

Committee Member

Heping Zhou, Ph.D

Committee Member

Jane Ko, Ph.D

Committee Member

Allan D. Blake, Ph.D

Keywords

Molluscum Contagiosum, MC160 Protein, Death Effector Domain, RxDL Motif, Interferon, NF-kB

Abstract

The Molluscum contagiosum virus (MCV) is a member of the Poxviridae family that causes benign skin lesions. MCV lesions persist on average for 8-12 months in otherwise healthy individuals. MCV lesions are characterized by reduced inflammation. The persistence and reduction of inflammation at the site of MCV lesions have been attributed to MCV immune evasion genes. MCV encodes two death effector domain (DED) containing proteins, MC159 and MC160. DEDs are found in cellular proteins such as FADD and procaspase-8. These cellular proteins are involved in several innate immune responses such as apoptosis and activation of interferon (IFN). Presumably, MC159 and MC160 bind to host DED-containing proteins as a means to prevent the formation of innate immune signaling complexes. The RxDL motif is conserved among several host and viral DED-containing proteins and has previously been shown to be required for protein function. The hypothesis of this study was the MC160 protein requires the RxDL motif to inhibit the activation of host inflammatory pathways. MCV mutants with mutated RxDL motifs were assessed for the ability to inhibit TBK1- and MAVS- induced activation of interferon-β. Surprisingly, the RxDL mutants retained the ability to inhibit IFN-β activation as assessed by the activity of a firefly luciferase gene under the control of the IFN-β enhancer. Therefore, the RxDL motif of the MC160 protein is not required for the inhibition of IFN activation.

 
 

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