Thesis
Investigating the role of transfer RNA regulation during murine gammaherpesvirus 68 infection
University of Iowa
Master of Science (MS), University of Iowa
Spring 2023
DOI: 10.25820/etd.007064
Abstract
Gammaherpesviruses (gHV) are lymphotropic DNA viruses, undergoing both lytic and latent infection. Kaposi sarcoma-associated herpesvirus (KSHV) is a gHV that causes lifelong infection in immunocompromised hosts, particularly those affected by AIDS. KSHV, like many viruses, alters the host gene expression landscape to increase virulence. Interestingly, transfer RNA (tRNA) synthesis is robustly stimulated by virus infection. There is a critical need to understand how KSHV alters the host gene expression landscape, including tRNA synthesis, to aid in creating novel therapeutics against KSHV. To study lytic infection in vitro, we utilize the functional and genetic homolog, murine gammaherpesvirus 68 (MHV68). Here, we investigate how MHV68 infection impacts tRNA expression. Following MHV68 infection, premature tRNA (pre-tRNA) and tRNA fragment (tRF) expression are upregulated following MHV68 infection, confirmed by using pre-tRNA-Tyr and 5’ tRF-Tyr as model tRNA species. Stem loop reverse transcription quantitative polymerase chain reaction (SL RT- qPCR) was optimized and successfully applied to quantitatively measure tRF expression during MHV68 infection. Further, functional consequences of altered pre-tRNA-Tyr and of 5’ tRF-Tyr expression during MHV68 infection were investigated. We found that tRF upregulation is dependent on post-entry viral gene expression but did not find a direct functional role for 5’ tRF-Tyr. Overall, these findings provide tools for further investigation of tRNA dysregulation that occurs as a result of gHV infections.
Details
- Title: Subtitle
- Investigating the role of transfer RNA regulation during murine gammaherpesvirus 68 infection
- Creators
- Ariana Rose Jimenez
- Contributors
- Jessica Tucker (Advisor)Wendy Maury (Committee Member)Richard Roller (Committee Member)
- Resource Type
- Thesis
- Degree Awarded
- Master of Science (MS), University of Iowa
- Degree in
- Interdisciplinary Studies in Immunology
- Date degree season
- Spring 2023
- DOI
- 10.25820/etd.007064
- Publisher
- University of Iowa
- Number of pages
- viii, 44 pages
- Copyright
- Copyright 2023 Ariana Rose Jimenez
- Language
- English
- Date submitted
- 04/24/2023
- Date approved
- 06/30/2023
- Description illustrations
- illustrations, tables, graphs
- Description bibliographic
- Includes bibliographical references (pages 40-44).
- Public Abstract (ETD)
- Kaposi’s Sarcoma-Associated Herpesvirus (KSHV) is a gammaherpesvirus (gHV) that causes lifelong infection in hosts that have a weakened immune system. KSHV infection interrupts the normal way cells process and communicate information amongst themselves and to other cells. We have seen that a class of ribonucleic acids (RNAs) that play a large role in making proteins, transfer RNAs (tRNAs), increase in expression after KSHV infection. Here, we study the role of a specific tRNA that undergoes cleavage into smaller RNAs. We assess if the increase in the tRNA expression and cleavage helps the virus replicate or if it helps the host fend off the virus. We predict that the tRNA dysregulation will restrict the virus from continuing to infect cells. We confirmed that tRNAs increase in expression after gHV infection, are cleaved into smaller RNAs when viral genes are expressed, and that specific tRNA-Tyr transcripts do not directly impact the virus. Future experiments need to be done to determine if tRNAs may hold promise in novel therapeutic strategies to block or treat gHV infection.
- Academic Unit
- Immunology Graduate Program
- Record Identifier
- 9984425390702771
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