Structural Analysis of the CVB3 Genomic 5' UTR

Advisor Information

William Tapprich

Location

225

Presentation Type

Oral Presentation

Start Date

1-3-2019 12:45 PM

End Date

1-3-2019 2:00 PM

Abstract

Coxsackievirus B3 (CVB3) is an important human pathogen and has been determined as a causative agent of myocarditis and pancreatitis. The single-stranded, positive-sense genomic RNA of CVB3 serves as a template for the production of the viral structural and nonstructural proteins. In absence of an m7G cap, the viral RNA has to rely on cap-independent translation initiation mechanisms. Similar to other enteroviruses, the CVB3 genome has a long, highly structured 5’ untranslated region (UTR), which has been identified as a determinant of viral virulence. The 5’ UTR houses a cloverleaf-like structure and a type I internal ribosome entry site, the proper folding of which is necessary for the interactions of the 5’ UTR with viral and host trans-acting factors and underlines the efficiency of viral replication. Here, we utilized a chemical probing method to characterize the secondary structure of the CVB3 5’ UTR. We propose a model with novel structural features including realignment of major domains and newly identified long-range interactions. Taken together, our work brings us closer to bridging the gap between structure and function in processes essential for the replicative success of CVB3 and related enteroviruses.

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Mar 1st, 12:45 PM Mar 1st, 2:00 PM

Structural Analysis of the CVB3 Genomic 5' UTR

225

Coxsackievirus B3 (CVB3) is an important human pathogen and has been determined as a causative agent of myocarditis and pancreatitis. The single-stranded, positive-sense genomic RNA of CVB3 serves as a template for the production of the viral structural and nonstructural proteins. In absence of an m7G cap, the viral RNA has to rely on cap-independent translation initiation mechanisms. Similar to other enteroviruses, the CVB3 genome has a long, highly structured 5’ untranslated region (UTR), which has been identified as a determinant of viral virulence. The 5’ UTR houses a cloverleaf-like structure and a type I internal ribosome entry site, the proper folding of which is necessary for the interactions of the 5’ UTR with viral and host trans-acting factors and underlines the efficiency of viral replication. Here, we utilized a chemical probing method to characterize the secondary structure of the CVB3 5’ UTR. We propose a model with novel structural features including realignment of major domains and newly identified long-range interactions. Taken together, our work brings us closer to bridging the gap between structure and function in processes essential for the replicative success of CVB3 and related enteroviruses.