Date of Award
Spring 5-1-2020
Degree Type
Thesis
Degree Name
MS Microbiology
Department
Biology
Advisor
Daniel B. Nichols, Ph.D
Committee Member
Tinchun Chu, Ph.D
Committee Member
Jane L. Ko, Ph.D
Keywords
Molluscum Contagiosum Virus, MC160, MC163, TNF-induced NF-κB activation, MAVS-induced IFN activation, RIP-induced NF-κB activation
Abstract
The Molluscum Contagiosum Virus (MCV) causes a common skin infection. A member of the Poxviridae family, MCV spreads through skin to skin contact and produces benign skin lesions that persist for months in otherwise healthy individuals. Despite its prevalence, MCV remains understudied, and its pathogenicity is poorly understood. Therefore, a more detailed understanding of MCV-host interactions is of great importance. The MCV genome encodes a variety of immune evasion molecules to antagonize host cell innate immune responses (IIRs). Two such MCV immune evasion molecule are the MC160 and MC163 proteins. MC160 contains two tandem death effector domains (DEDs). DEDs are found in both cellular and viral proteins and are known to interact with a variety of apoptotic and inflammatory signaling molecules associated with antiviral responses. MC160 expression inhibits a variety of pathways including TNF-induced NF-κB activation and induction of type I IFNs. MC163 expression antagonizes events associated with host cell apoptotic responses. In the current thesis, the goal was to characterize and identify the molecular mechanisms through which MC160 and MC163 exert their effects in the cell. Using truncated MC160 mutants, we determine that both DEDs of MC160 are required to inhibit activation of type I IFNs. Additionally, MC163 expression blocks activation of NF-κB induced by the overexpression of adapter molecule RIP. Presumably, both MC160 and MC163 expression during infection contribute to virulence by dampening the host immune responses, thus increasing the persistence of an MCV infection.
Recommended Citation
Suarez, Catherine D., "The Molluscum Contagiosum Virus targets host innate immune signaling networks at multiple points using viral proteins MC160 and MC163" (2020). Seton Hall University Dissertations and Theses (ETDs). 2768.
https://scholarship.shu.edu/dissertations/2768
