Date of Award
Daniel Brian Nichols, Ph.D.
Tin-Chun Chu, Ph.D.
Constantine Bitsaktsis, Ph.D.
Angela Klaus, Ph.D.
Heping Zhou, Ph.D.
Molluscum contagiosum virus, MC160, MAVS
The Molluscum Contagiosum Virus (MCV), belongs to a family of large DNA viruses called Poxviridae. MCV causes a common skin infection resulting in benign neoplasms. 122 million cases of MC were reported in 2010. The virus is not primarily lethal, though fatalities have occurred due to secondary bacterial infections. Even with the high volume of reported cases, MCV is very much understudied, and its pathogenicity is not well understood. Thus, with that in mind, a more in-depth understanding of the MCV-host interactions is a priority. Presumably during infection, MCV utilizes immune evasion molecules to inhibit activation of the host pro-inflammatory signal pathways allowing the infection to persist. However, only nine of a predicted 77 immune evasion molecules, encoded by the MCV genome, have been characterized. This study focuses on one in particular, the MC160 protein. MC160 contains a pair of death effector domains (DEDs). MC160 expression inhibits various innate immune responses (IIRs), such as TNFα-induced NF-κB activation and MAVS-mediated activation of type I interferons (IFN). The first death effector domain (DED1) inhibits the activation of IRF3, a vital transcription factor in the activation of type I IFNs. To further discover the region(s) of interest within the first DED1 of MC160 that are required for MAVS-induced IRF3 inhibition, five MC160 truncation mutants were generated, by deleting predicted α- helixes from DED1. Constructs expressing truncated MC160 mutants were evaluated for the ability to inhibit MAVS-mediated IFNβ activation using the dual luciferase activity. Preliminary data, from transfection of HEK 293T cells with MC160 truncation mutants identified the second α-helix as being critical for the MC160 protein’s ability to inhibit activation of IFNβ. By identifying the region of MC160 required to antagonize host immune signaling, we hope to gain a better understanding of how MC160 expression antagonizes this important IIR.
Estanbouli, Henri, "Mutational Analysis of the Molluscum Contagiosum Virus MC160 protein" (2017). Seton Hall University Dissertations and Theses (ETDs). 2477.
Available for download on Tuesday, December 18, 2018