Date of Award

Spring 4-26-2024

Degree Type


Degree Name

MS Microbiology




Daniel Brian Nichols, PhD


Constantine Bitsaktsis, PhD

Committee Member

Erik Hill, PhD

Committee Member

Jessica Cottrell, PhD


Moluscum Contagiosum, MCV, Poxvirus, MC160, MC159


Molluscum Contagiosum Virus (MCV) is a human skin pathogen that causes persistent, benign lesions on the epidermis after infected skin to skin contact. The virus dedicates 30% of its genome to immune evasion genes to dampen the host cell’s response. The cytoplasm is an important area of replication for the virus and also houses key immune pathogen recognition receptors such as cyclic GMP-AMP synthase (cGAS) that detect Pathogen Associated Molecular Patterns, such as cytoplasmic dsDNA. MCV proteins MC160 and MC159 modulate both the cGAS/STING pathways for cytoplasmic dsDNA detection and the MAVS pathways for dsRNA detection. Both pathways ultimately end up with the production of Type I interferons. Despite structural similarities, the MC160 and MC159 have noticeably different phenotypes. MC160 expression dampens both MAVS and cGAS/STING mediated activation of type I interferons. The MC159 protein on the other hand inhibits the MAVS pathway but surprisingly enhances the cGAS/STING pathway under conditions tested in this study. To better understand the mechanisms of MCV immune evasion proteins, this study characterized the expression of MC160 and MC159 proteins alone on MAVS- and cGAS/STING induced activation of transcription factors required for binding the IFN enhancer element. When cGAS/STING were overexpressed, co-expression with the MC159 protein upregulated the activation of the type I interferon enhancer as well as the transcription factor NF-κB. The MC160 protein maintained its inhibiting attribute on both sides of the immune pathways (cGAS/STING or MAVS). The data generated in this thesis highlights different functions of the MC160 and MC159 protein and suggests both proteins would be required to mitigate the full scope of the host cell innate immune response to viral nucleic acids.

Available for download on Monday, May 01, 2034