ORCID
0009-0009-7884-7918
Date of Award
Fall 2025
Language
English
Embargo Period
9-9-2026
Document Type
Dissertation
Degree Name
Doctor of Philosophy (PhD)
College/School/Department
Department of Biological Sciences
Program
Biology
First Advisor
Cara Pager
Committee Members
Andy Berglund, Tom Begley, Kaalak Reddy
Keywords
Modifications, ZIKV, Immune Response
Subject Categories
Biology
Abstract
Zika virus (ZIKV) remains a significant public health concern due to major gaps in our understanding of its infection mechanisms and immune evasion strategies. Despite its link to severe complications such as microcephaly and Guillain-Barré Syndrome (GBS), no vaccine or targeted antiviral therapies exist. Compounding this concern is the expanding habitat of ZIKV-carrying mosquito vectors, driven by climate change, which increases the risk of future outbreaks in previously unaffected regions.
One promising area of investigation involves post-transcriptional modifications (PTMs) chemical alterations to RNA that influence its stability, translation, and function. Although over 170 PTMs have been identified, their roles remain largely unexplored, especially in viral pathogenesis. Recent research has begun to link specific RNA modifications, such as N4-acetylcytidine (ac4C), to viral infections including HIV-1 and EV71. These modifications may represent a novel layer of host-virus interaction through which viruses evade immune detection.
Our work demonstrates that ZIKV infection alters the landscape of RNA modifications, notably showing a consistent decrease in ac4C. We identified that the ac4C "writer" enzyme, NAT10, is crucial for an effective host immune response. In NAT10-deficient cells, ZIKV infection resulted in elevated viral RNA, protein, and titers, as well as accelerated degradation of key immune effectors such as IFIT1 and MX1. This suggests that NAT10-mediated ac4C plays a protective role, helping the host sustain an effective innate immune response during ZIKV infection.
These findings highlight a previously underappreciated axis of viral regulation and immune modulation, with broader implications for understanding RNA virus infections. By linking epitranscriptomic dynamics to immune function, this work lays critical groundwork for future therapeutic strategies targeting RNA modifications during viral infections.
License
This work is licensed under a Creative Commons Attribution 4.0 International License.
Recommended Citation
Gianola, Shawn, "NAT10 Stabilizes Immune Response Factors Aiding with Cellular Immune Response to Zika Virus Infection" (2025). Electronic Theses & Dissertations (2024 - present). 298.
https://scholarsarchive.library.albany.edu/etd/298