Date of Award

Summer 2018

Document Type

Thesis

Degree Name

Master of Science (MS)

Department

Biological Sciences

Committee Director

Girish Neelakanta

Committee Member

Hameeda Sultana

Committee Member

Emelia Oleszak

Abstract

Epigenetics is the heritable series of covalent modifications that affect chromatin structure, gene expression, and protein function. Methylation is one such epigenetic modification that involves the addition of chemical modifying entities, such as methyl groups, on nucleic acids or proteins. Recent studies have reported that Zika virus (ZIKV) modulates methylation of human and viral RNA important for its replication in vertebrate cells. However, little is known whether ZIKV exerts methylation in arthropod vectors. In this study, I show that ZIKV modulates S-adenosyl methionine (SAMe) synthase, an enzyme involved in the production of SAMe, and histone methylation for its survival in Aedes albopictus derived C6/36 cell line. Quantitative real-time PCR (QRT-PCR) and immunoblotting analysis revealed increased amounts of the mosquito SAMe synthase at both RNA and protein levels, respectively, in ZIKV-infected C6/36 cells at day 1 post infection (p.i.) in comparison to uninfected controls. Increase in the intracellular SAMe levels was noted in ZIKV-infected C6/36 cells at day 1p.i. in comparison to uninfected controls. In addition, significant increased amounts of Enhancer of zeste homolog 2 (EZH2) histone methyl transferase-like gene transcripts and histone tri-methylation (H3K27me3) were noted in ZIKV-infected C6/36 cells in comparison to uninfected controls. Exogenous treatment with SAMe showed significant increased viral burden and expression of EZH2 transcripts in ZIKV-infected C6/36 cells at day 1 p.i. in comparison to mock-treated controls. Treatment with DZNep, a known EZH2 inhibitor, revealed a decrease in H3K27me3 and ZIKV burden in ZIKV-infected C6/36 cells. In summary, my data suggests ZIKV-associated modulation of SAMe cycle and H3K27me3, critical for its survival in mosquitoes.

DOI

10.25777/dqx5-vn94

Available for download on Saturday, October 03, 2020

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