Structural Analysis of Genomic RNA from Avirulent and Virulent Strains of Coxsackievirus B3

Presenter Information

Lydia PhillipsFollow

Advisor Information

Dr. William Tapprich

Location

MBSC 222

Presentation Type

Oral Presentation

Start Date

6-3-2020 9:00 AM

End Date

6-3-2020 10:15 AM

Abstract

ABSTRACT: Structural Analysis of Genomic RNA from Avirulent and Virulent Strains of Coxsackievirus B3

Enteroviruses are a large and well-studied genus of non-enveloped viruses in the Picornaviridae family responsible for diseases such as polio, hand foot and mouth disease, and the common cold, among others. Coxsackievirus B3 (CVB3), a cousin to poliovirus, is also responsible for severe human disease, including pancreatitis, myocarditis, and type 1 diabetes. A unique advantage of studying CVB3 is the existence of a naturally occurring strain (CVB3/GA) which displays no known pathogenicity. A key region of enteroviral RNA genomes, called the 5’ untranslated region (5’ UTR) shows a conserved organization of six structural domains. Domain II and the linking region between domain I and domain II has been shown to be a determinant of virulence in many enteroviruses. The primary difference between avirulent CVB3/GA and the virulent strains of CVB3 is sixty-three nucleotide substitutions in the 5’UTR, four of which cause a change in predicted base pairing and ultimately the structure. Although a theoretical secondary structure of CVB3/GA was proposed and chemical probing in our lab has confirmed some of the theoretical structures, work is needed to accurately determine the structural differences in the 5’UTR of genomes from virulent and nonvirulent viruses. We employ a novel method called 2′-hydroxyl acylation analyzed by primer extension and mutational profiling (SHAPE-MaP) for the comparative analysis of the 5’UTR from virulent CVB3/28 and avirulent CVB3/GA. Understanding the structural differences between virulent and avirulent strains is vital for future development of vaccines and other viral treatments.

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Mar 6th, 9:00 AM Mar 6th, 10:15 AM

Structural Analysis of Genomic RNA from Avirulent and Virulent Strains of Coxsackievirus B3

MBSC 222

ABSTRACT: Structural Analysis of Genomic RNA from Avirulent and Virulent Strains of Coxsackievirus B3

Enteroviruses are a large and well-studied genus of non-enveloped viruses in the Picornaviridae family responsible for diseases such as polio, hand foot and mouth disease, and the common cold, among others. Coxsackievirus B3 (CVB3), a cousin to poliovirus, is also responsible for severe human disease, including pancreatitis, myocarditis, and type 1 diabetes. A unique advantage of studying CVB3 is the existence of a naturally occurring strain (CVB3/GA) which displays no known pathogenicity. A key region of enteroviral RNA genomes, called the 5’ untranslated region (5’ UTR) shows a conserved organization of six structural domains. Domain II and the linking region between domain I and domain II has been shown to be a determinant of virulence in many enteroviruses. The primary difference between avirulent CVB3/GA and the virulent strains of CVB3 is sixty-three nucleotide substitutions in the 5’UTR, four of which cause a change in predicted base pairing and ultimately the structure. Although a theoretical secondary structure of CVB3/GA was proposed and chemical probing in our lab has confirmed some of the theoretical structures, work is needed to accurately determine the structural differences in the 5’UTR of genomes from virulent and nonvirulent viruses. We employ a novel method called 2′-hydroxyl acylation analyzed by primer extension and mutational profiling (SHAPE-MaP) for the comparative analysis of the 5’UTR from virulent CVB3/28 and avirulent CVB3/GA. Understanding the structural differences between virulent and avirulent strains is vital for future development of vaccines and other viral treatments.