Date of Award

Spring 5-14-2016

Degree Type

Thesis

Degree Name

MS Microbiology

Department

Biology

Advisor

Daniel Nichols, Ph.D

Committee Member

Angela Klaus, Ph.D

Committee Member

Jane L. Ko, Ph.D

Committee Member

Constantine Bitsaktsis, Ph.D

Keywords

Molluscum contagiosum virus, MC163, Apoptosis

Abstract

Molluscum Contagiosum Virus (MCV) is an obligate human, tumorigenic poxvirus which causes benign skin neoplasms. Reduced inflammation during an MCV infection has been attributed to production of MCV immune evasion molecules (IEMs). IEMs antagonize host immune responses allowing MCV to evade the host immune system and reprogram the host cell for viral growth. MCV IEMs alter apoptosis (MC159, MC160), deregulate the cell cycle targeting retinoblastoma (MC007), and produce a chemokine homolog (MC148). Bioinformatics analysis identified MC163, as another potential host-interacting protein. Further analysis of MC163 resulted in the identification of a mitochondrial localization sequence, putative superoxide dismutase (SOD)-like Cu2+/Zn2+ metal binding domain, a transmembrane domain and a large C-terminal domain that contains no identified homology to other viral or host proteins. Confocal microscopy was utilized to verify the predicted mitochondrial localization. MC163 was detected at the mitochondria, whereas a truncated MC163 lacking the mitochondria localization sequence was diffused throughout the cell. Mitochondria are important moderators in apoptotic and anti-viral signaling. Many viral proteins that localize to the mitochondria affect mitochondria immune signaling pathways such as apoptosis. Preliminary data suggests that expression of MC163 inhibits TNF-induced mitochondrial membrane permeabilization MMP. Therefore, MC163 expression may contribute to MCV immune evasion by antagonizing apoptotic signaling events.

Included in

Virology Commons

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