Investigation of 5’ NTR Domain II Secondary Structure in Virulent Coxsackievirus B3/28
Advisor Information
William Tapprich
Location
Milo Bail Student Center Ballroom
Presentation Type
Poster
Start Date
8-3-2013 1:00 PM
End Date
8-3-2013 4:00 PM
Abstract
Coxsackievirus B3 (CVB3) is an Enterovirus from the Picornaviridae family that contains a positive sense RNA genome. CVB3 is a known pathogenic agent to cause myocarditis and pancreatitis. The genome of CVB3 includes a 748 base 5’ untranslated region (5’UTR) organized into six highly structured domains that studies have proven are important to viral efficiency. Comparative sequence analysis shows the nucleotide stretches in the 5’ NTR Domain II displays significant variability among enteroviruses. An example of Domain II variability is nucleotide differences found in cardiovirulent CVB3/28 and noncardiovirulent CVB3/GA. These findings, together with studies of chimeric viral genomes, lead to the hypothesis that Domain II could be a virulence determinant. Extensive studies investigating secondary and tertiary interactions occurring in the 5’NTR of CVB3/28 have been conducted to achieve a better understanding of Domain II structure. Results from our laboratory show dramatic structural differences in Domain II of CVB3/28 than that found in CVB3/GA. We have constructed site specific mutations in the CVB3/28 genome within this highly variable region of Domain II to test the detailed relationship between sequence and structure in the 5’ NTR. The goal of our investigation through chemical probing techniques is to gain supporting evidence of structural transitions occurring as a result of alterations in the nucleotide sequence of Domain II and its role in CVB3 virulence.
Investigation of 5’ NTR Domain II Secondary Structure in Virulent Coxsackievirus B3/28
Milo Bail Student Center Ballroom
Coxsackievirus B3 (CVB3) is an Enterovirus from the Picornaviridae family that contains a positive sense RNA genome. CVB3 is a known pathogenic agent to cause myocarditis and pancreatitis. The genome of CVB3 includes a 748 base 5’ untranslated region (5’UTR) organized into six highly structured domains that studies have proven are important to viral efficiency. Comparative sequence analysis shows the nucleotide stretches in the 5’ NTR Domain II displays significant variability among enteroviruses. An example of Domain II variability is nucleotide differences found in cardiovirulent CVB3/28 and noncardiovirulent CVB3/GA. These findings, together with studies of chimeric viral genomes, lead to the hypothesis that Domain II could be a virulence determinant. Extensive studies investigating secondary and tertiary interactions occurring in the 5’NTR of CVB3/28 have been conducted to achieve a better understanding of Domain II structure. Results from our laboratory show dramatic structural differences in Domain II of CVB3/28 than that found in CVB3/GA. We have constructed site specific mutations in the CVB3/28 genome within this highly variable region of Domain II to test the detailed relationship between sequence and structure in the 5’ NTR. The goal of our investigation through chemical probing techniques is to gain supporting evidence of structural transitions occurring as a result of alterations in the nucleotide sequence of Domain II and its role in CVB3 virulence.