Molecular mechanisms of Respiratory Syncytial Virus regulation
Date
2022-05
Authors
Thornhill, Elena M
Major Professor
Advisor
Verhoeven, David
Miller, Cathy
Miller, Allen
McGill, Jodi
Moss, Walter
Committee Member
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Abstract
Respiratory Syncytial Virus (RSV) is a widespread respiratory pathogen with the capacity to cause severe disease in vulnerable populations. Despite the significant morbidity caused by RSV in the world’s populace, there is very little knowledge about the basic science of this virus. Most of the research published focuses on the pathogenesis and immunologic response of/to the virus or vaccine or therapeutic development. Any new information on how RSV molecularly regulates its precisely timed lifecycle is valuable for future RSV inhibition. Described herein are molecular mechanisms by which RSV regulates its replication, giving us insights into potential new avenues of viral therapies. The F gene was shown to have secondary RNA structure necessary for RSV replication through computational and experimental analysis. Further computational analysis showed multiple conserved structures throughout the RSV genome and transcriptome that may also impact regulation of the lifecycle of RSV and will need to be studied further in the future. Additionally, coinfection studies with SARS-CoV2, and its Nsp1 protein, revealed that a region of the RSV M2 mRNA is affected by Nsp1 ablating M2-2 expression and attenuating viral replication when coinfected with SARS-CoV2. Finally, analysis of RSV infection of blood neutrophils showed a lack of Ns1 and Ns2 expression, which in vivo likely leads to a non-permissive infection. From this work, an investigation to determine the differences in the cellular environment in neutrophils that leads to this lack of Ns1 and Ns2 compared to epithelial cells is warranted. All three of these discoveries will open new avenues of therapy creation by structure targeting, generating inhibitory molecules to prevent M2-2 expression, and targeting the inhibitory antiviral response viral proteins of RSV.
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Microbiology
Type
article