Date of Award

Summer 8-15-2017

Author's School

Graduate School of Arts and Sciences

Author's Department

Biology & Biomedical Sciences (Computational & Systems Biology)

Degree Name

Doctor of Philosophy (PhD)

Degree Type

Dissertation

Abstract

Caenorhabditis elegans is a powerful model organism that has elucidated many biological questions in the fields of genetics, development, and neurobiology. In addition, C. elegans has been used in the past decade to investigate host-pathogen interactions with bacteria and fungi. The recent identification of nematode viruses that naturally infect C. elegans and Caenorhabditis briggsae provides a unique opportunity to define host-virus interactions in these model hosts.

This dissertation first explored the transcriptional response of C. elegans and C. briggsae to virus infection by RNA-seq. I identified a total of 320 differentially expressed genes (DEGs) in C. elegans following Orsay virus infection. The DEGs were mostly genes of unknown function. Interestingly, many DEGs that responded to Orsay virus infection were similar to those induced by Nematocida parisii infection, which is a natural microsporidia pathogen of C. elegans that like Orsay virus infects intestinal cells. Furthermore, comparison of the Orsay virus DEGs in C. elegans to Santeuil virus DEGs in C. briggsae identified 58 C. elegans genes whose orthologs were likewise differentially expressed in C. briggsae, thereby defining an evolutionarily conserved response to viral infection.

A systematic effort that utilized multiple approaches from the available genetic tools was carried out in C. elegans to determine if the evolutionarily conserved DEGs impacted Orsay virus replication either positively or negatively. I found two genes that putatively interact with Orsay virus. The first gene was T27E7.6, a gene of unknown function, that may play an antiviral role. The second gene, zip-10, a nematode transcription factor, may be a proviral gene that facilitates Orsay virus infection. Neither gene was previously implicated in host-virus interactions. The identification of the virus response genes and the discovery of genes that alter Orsay virus infection of C. elegans provide a foundation for future studies of host virus interactions in this model system.

Language

English (en)

Chair and Committee

David Wang

Committee Members

Tim Schedl, Barak Cohen, Deborah Lenschow, Michael Nonet,

Comments

Permanent URL: https://doi.org/10.7936/K71J996W

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