"IDENTIFICATION OF LNCRNAS INVOLVED IN THE HOST RESPONSE TO VENEZUELAN " by Mahgol Behnia
 

Biomedical Sciences ETDs

Publication Date

Fall 12-1-2024

Abstract

Venezuelan equine encephalitis virus (VEEV) is an enveloped positive-sense RNA virus in the alphavirus genus of the Togaviridea family, that causes encephalitis in humans and equids. Currently no FDA-approved vaccine or treatment is available for human use, emphasizing the importance of studying host-VEEV interaction. lncRNAs are regulatory RNAs involved in modulation of antiviral pathways during viral infections. Here we report differential lncRNAs expression in primary mouse astrocytes and neurons during non-pathogenic (TC-83) but not pathogenic (TrD) VEEV infection. We further demonstrated that suppression of four lncRNAs increased TC-83 replication, with lncRNA small nucleolar RNA host gene 15 (Snhg15) increasing TC-83 replication by more than 10-fold. Further investigation into Snhg15 function during TC-83 infection showed a decreas in expression of proinflammatory chemokines after Snhg15 knockdown in TC-83-infected primary mouse astrocytes. KEGG pathway analysis further confirmed significant suppression of antiviral signaling pathways during TC-83 infection after Snhg15 knockdown in these cells. Investigation of the regulatory function of Snhg15 on the NF-kB signaling pathway did not show any changes in the activation of this pathway after Snhg15 suppression, suggesting that Snhg15 modulates VEEV infection using a different mechanism. Further investigations are needed to unravel the mechanism by which Snhg15 regulates VEEV infection.

Keywords

VEEV, lncRNA, Alphavirus, Noncoding RNA, Host-virus interaction

Document Type

Dissertation

Language

English

Degree Name

Biomedical Sciences

Level of Degree

Doctoral

Department Name

Biomedical Sciences Graduate Program

First Committee Member (Chair)

Amy Gardiner

Second Committee Member

Steven Bradfute

Third Committee Member

Alison Kell

Fourth Committee Member

Viswanathan Palanisamy

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