The substitution U475 arrow right C with Sabin3-like mutation within the IRES attenuate Coxsackievirus B3 cardiovirulence

• Published in: Molecular biotechnology Vol. 36; no. 1; pp. 52 - 60
• Main Authors: M'hadheb-Gharbl, M B, Paulous, S, Aounl, M, Kean, K M, Gharbi, J
• Format: Journal Article
• Language: English
• Published: 01.05.2007
• Subjects: Coxsackievirus B3; Poliovirus
• ISSN: 1073-6085

The Sabin3 mutation in the viral RNA plays an important role in directing attenuation phenotype of Sabin vaccine strain of poliovirus type 1 (PV1). We previously described that Sabin3-like mutation Introduced in Coxsackievirus B3 (CVB3) genome led to a defective mutant. However, this mutation do not led to destruction of secondary structure motif C within the stem-loop V of CVB3 RNA because of the presence of one nucleotide difference (C arrow right U) in the region encompassing the Sabin3 mutation at nucleotides 471 of PV1 and 475 of CVB3 RNA. In order to reproduce the same sequence of PV1 sabln3 vaccine strain, we introduce in this study an additional mutation (U475 arrow right C) to CVB3 Sabin3-like mutant. Our results demonstrated that Sabin3-like+C mutant displayed a decreased translation initiation defects when translated in cell-free system. This translation initiation defect was correlated with reduced yields of infectious virus particles in HeLa cells in comparison with Sabin3-like mutant and wild-type CVB3 viruses. Inoculation of Swiss mice with mutant viruses resulted in no inflammatory heart disease when compared to heart of mice Infected with wild-type. Theses findings indicate that the double mutant could be exploited for the development of a live attenuated vaccine against CVB3.