title: Major alteration in coxsackievirus B3 genomic RNA structure distinguishes a virulent strain from an avirulent strain.
abstract: Coxsackievirus B3 (CV-B3) is a cardiovirulent enterovirus that utilizes a 5' untranslated region (5'UTR) to complete critical viral processes. Here, we directly compared the structure of a 5'UTR from a virulent strain with that of a naturally occurring avirulent strain. Using chemical probing analysis, we identified a structural difference between the two 5'UTRs in the highly substituted stem-loop II region (SLII). For the remainder of the 5'UTR, we observed conserved structure. Comparative sequence analysis of 170 closely related enteroviruses revealed that the SLII region lacks conservation. To investigate independent folding and function, two chimeric CV-B3 strains were created by exchanging nucleotides 104-184 and repeating the 5'UTR structural analysis. Neither the parent SLII nor the remaining domains of the background 5'UTR were structurally altered by the exchange, supporting an independent mechanism of folding and function. We show that the attenuated 5'UTR lacks structure in the SLII cardiovirulence determinant.
authors: Biology Department, University of Nebraska at Omaha, Omaha, NE 68182, USA.
authors: Jerome
authors: J
authors: Prusa
authors: Department of Family Medicine, University of Nebraska Medical Center, Omaha, NE 68198, USA.
authors: Johanna
authors: J
authors: Missak
authors: Genetics, Cell Biology and Anatomy, University of Nebraska Medical Center, Omaha, NE 68198, USA.
authors: Jeff
authors: J
authors: Kittrell
authors: Department of Pathology, University of Colorado Anshutz Medical Campus, Denver, CO 80045, USA.
authors: John J
authors: JJ
authors: Evans
authors: Biology Department, University of Nebraska at Omaha, Omaha, NE 68182, USA wtapprich@unomaha.edu.
authors: William E
authors: http://orcid.org/0000-0002-7744-7658
authors: WE
authors: Tapprich
mesh_terms: D020121:5' Untranslated Regions; D029822:Enterovirus B, Human / Q000235:genetics* / Q000472:pathogenicity; D016679:Genome, Viral; D009690:Nucleic Acid Conformation; D012367:RNA, Viral / Q000737:chemistry*; D014774:Virulence
chemical_list: D020121:5' Untranslated Regions; D012367:RNA, Viral