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ARS Home » Northeast Area » Orient Point, New York » Plum Island Animal Disease Center » Foreign Animal Disease Research » Research » Publications at this Location » Publication #343415

Research Project: Intervention Strategies to Support the Global Control and Eradication of Foot-and-Mouth Disease Virus (FMDV)

Location: Foreign Animal Disease Research

Title: Differential replication of foot-and-mouth disease viruses in mice determine lethality

Author
item Cacciabue, Marco - Instituto Nacional De Tecnologia Agropecuaria
item Garcia-nunez, Maria - Instituto Nacional De Tecnologia Agropecuaria
item Delgado, Fernando - Instituto Nacional De Tecnologia Agropecuaria
item Curra, Anabella - Instituto Nacional De Tecnologia Agropecuaria
item Marrero, Ruben - Instituto Nacional De Tecnologia Agropecuaria
item Molinari, Paula - Instituto Nacional De Tecnologia Agropecuaria
item Rieder, Aida - Elizabeth
item Carrillo, Elisa - Instituto Nacional De Tecnologia Agropecuaria
item Gismondi, Maria - Instituto Nacional De Tecnologia Agropecuaria

Submitted to: Virology
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: 6/12/2017
Publication Date: 6/22/2017
Citation: Cacciabue, M., Garcia-Nunez, M.S., Delgado, F., Curra, A., Marrero, R., Molinari, P., Rieder, A.E., Carrillo, E., Gismondi, M.I. 2017. Differential replication of foot-and-mouth disease viruses in mice determine lethality. Virology. 509:195-204. doi: 10.1016/j.virol.2017.06.012.

Interpretive Summary: Since the discovery in 1897 that foot-and-mouth disease (FMD) was caused by a viral agent, scientific efforts have focused on the development of control measures of this highly devastating disease. In this study, we further characterize two FMDV A/Arg/01 variants in terms of pathogenicity in adult mice and replication in cell culture. Mutations found between a highly pathogenic and low pathogenic FMD viruses determined the outcome of viral replication in mice and contributing to the differential phenotypes observed.

Technical Abstract: Adult C57BL/6J mice have been used to study foot-and-mouth disease virus (FMDV) biology. In this work, two variants of an FMDV A/Arg/01 strain exhibiting differential pathogenicity in adult mice were identified and characterized: a non-lethal virus (A01NL) caused mild signs of disease, whereas a lethal virus (A01L) caused dead within 24-48 h independently of the dose used. Both viruses caused a systemic infection with pathological changes in the exocrine pancreas. Virus A01L reached higher viral loads in plasma and organs of inoculated mice as well as increased replication in an ovine kidney cell line. Complete consensus sequences revealed 6 non-synonymous changes between A01L and A10NL genomes that might be linked to replication differences, as suggested by in silico prediction studies. Our results highlight the biological significance of discrete genomic variations and reinforce the usefulness of this animal model to study viral determinants of lethality.