Enhanced IRES activity by the 3’UTR element determines the virulence of FMDV isolates

Authors: GARCIA-NUNEZ, SOLEDAD - Instituto Nacional Tecnologia Agropecuaria; GISMONDI, MARIA - Instituto Nacional Tecnologia Agropecuaria; KONIG, GUIDO - Instituto Nacional Tecnologia Agropecuaria; BERINSTEIN, ANALIA - Instituto Nacional Tecnologia Agropecuaria; TABOGA, OSCAR - Instituto Nacional Tecnologia Agropecuaria; Rieder, Aida - Elizabeth; MARTINEZ-SALAS, ENCARNACION - University Of Madrid; CARRILLO, ELISA - Instituto Nacional Tecnologia Agropecuaria

Submitted to: Virology
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: 10/18/2013
Publication Date: 1/5/2014
Publication URL: http://handle.nal.usda.gov/10113/59456
Citation: Garcia-Nunez, S., Gismondi, M.I., Konig, G., Berinstein, A., Taboga, O., Rieder, A.E., Martinez-Salas, E., Carrillo, E. 2014. Enhanced IRES activity by the 3’UTR element determines the virulence of FMDV isolates. Virology. 448:303-313.

Interpretive Summary: Foot and mouth disease virus (FMDV) causes a devastating disease (FMD) in livestock and represents a major threat to US agriculture exports and food security. The results described in this study contribute to a better understanding of the virulence determinant of field FMDVs. We have hypothesized that defined sequences of the FMDV genome are responsible for the different biological and pathological properties exhibited by viruses responsible for FMD outbreaks in Argentina in 2000 and 2001. Using biological and genetics approaches we show that a region near the 5´end of the FMDV genome is modulated by distant sequences contained at the 3´end of the viral genome.

Technical Abstract: A reverse genetics approach was used to identify viral genetic determinants of the differential virulence displayed by two field foot-and-mouth disease virus (FMDV) strains (A/Arg/00 and A/Arg/01) isolated in Argentina during the 2000-2001 epidemics. A molecular clone of A/Arg/01 strain and viral chimeras containing the Sfragment or the internal ribosome entry site (IRES) of A/Arg/00 in the A/Arg/01 backbone were constructed and characterized. The IRES appeared as a determining factor of the lower level of A/Arg/00 replication in cell culture. High-throughput RNA probing revealed structural differences between both IRESs. Translation experiments using either synthetic viral RNAs (in vitro) or bicistronic plasmids (in vivo) showed that these IRESs’ activities differ when the viral 3’ untranslated region (UTR) is present, suggesting that their function is differentially modulated by this region. This work provides experimental evidence supporting the role of the IRES-3’ UTR modulation in determining the level of FMDV replication in field strains.