Identification of lncRNAs Involved in the Host Response to Venezuelan Equine Encephalitis Virus Infection

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.