Major alteration in coxsackievirus B3 genomic RNA structure distinguishes a virulent strain from an avirulent strain

作者:Prusa Jerome; Missak Johanna; Kittrell Jeff; Evans John J; Tapprich William E*
来源:Nucleic Acids Research, 2014, 42(15): 10112-10121.
DOI:10.1093/nar/gku706

摘要

Coxsackievirus B3 (CV-B3) is a cardiovirulent enterovirus that utilizes a 5%26apos; untranslated region (5%26apos; UTR) to complete critical viral processes. Here, we directly compared the structure of a 5%26apos; 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%26apos; UTRs in the highly substituted stem-loop II region (SLII). For the remainder of the 5%26apos; 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%26apos; UTR structural analysis. Neither the parent SLII nor the remaining domains of the background 5%26apos; UTR were structurally altered by the exchange, supporting an independent mechanism of folding and function. We show that the attenuated 5%26apos; UTR lacks structure in the SLII cardiovirulence determinant.

  • 出版日期2014