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

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 S-fragment 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.

Baculovirus treatment fully protects mice against a lethal challenge of FMDV.

Foot-and-mouth disease virus (FMDV) causes a highly contagious and economically devastating disease that affects cattle, swine, goat and sheep among others. FMDV is able to overcome the initial host innate immune response by inhibiting the induction of antiviral molecules at both the transcriptional and the translational levels. It has been demonstrated that FMDV A/Arg/2001 causes the death of adult C57Bl/6 mice within 72h. We evaluated the capacity of Autographa californica nuclear polyhedrosis virus (AcNPV), an insect virus with potent innate immunostimulating effects, to promote early protection against FMDV A/Arg/2001 challenge in C57Bl/6 mice. Groups of 8-9 weeks old female mice were injected intravenously with AcNPV and challenged with a lethal dose of FMDV at different times post-administration. Our results showed that pretreatment of mice with a single injection of AcNPV 3h or 3 days before FMDV challenge resulted in complete abrogation of mortality and complete or partial suppression of viremia, respectively. Furthermore, no signs of disease were observed. AcNPV could be a valuable tool to improve the design of a novel vaccine that protects as an adjuvant at early times post-vaccination.

Differences in the virulence of two strains of Foot-and-Mouth Disease Virus Serotype A with the same spatiotemporal distribution.

During the 2000-2001 epidemic of Foot-and-Mouth Disease Virus (FMDV) in Argentina, two FMDV serotype A viruses were identified among others. Since different pathogenic properties between these virus strains were noticed in cattle, we evaluated several biological properties and features of FMDV A/Arg/00 and FMDV A/Arg/01 in order to compare these viruses in terms of virulence and pathogenicity. Our results indicate that FMDV A/Arg/00 grows less efficiently than FMDV A/Arg/01, exemplified by smaller sized plaques, retarded one-step growth curves and overall low viral yields. Also, FMDV A/Arg/00 displayed the lowest specific infectivity in suckling mice requiring 50-fold more infectious particles than FMDV A/Arg/01 to generate a LD50 in suckling mice. Finally, FMDV A/Arg/00 did not cause death in adult C57Bl/6 mice even at high doses (10(7)-10(6)PFU) whereas FMDV A/Arg/01 resulted lethal in doses as low as 10(2)PFU. Overall, we were able to demonstrate that these virus strains differ from each other in terms of virulence and pathogenicity.