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Title: FOOT-AND-MOUTH DISEASE UTILIZES AN AUTOPHAGIC PATHWAY DURING VIRAL REPLICATION

Author
item Baxt, Barry
item O'DONNELL, VIVIAN - UNIV OF CONNECTICUT
item PACHECO-TOBIN, JUAN - OAKRIDGE INST SCIENCE EDU
item Larocco, Michael
item JACKSON, WILLIAM - STANFORD UNIVERSITY

Submitted to: Meeting Abstract
Publication Type: Abstract Only
Publication Acceptance Date: 5/30/2006
Publication Date: 7/15/2006
Citation: Baxt, B., O'Donnell, V.K., Pacheco-Tobin, J.M., Larocco, M.A., Jackson, W. Foot-and-mouth disease utilizes an autophagic pathway during viral replication. American Society for Virology Annual Meeting. 2006. p. 176

Interpretive Summary:

Technical Abstract: Foot-and-mouth disease virus (FMDV) is the type species of the Aphthovirus genus, of the family Picornaviridae. Infection with positive-strand RNA viruses results in the rearrangement of intracellular membranes into viral replication complexes (VRC) which are the sites of viral RNA replication. Cellular autophagy has been proposed to be a mechanism of VRC formation for a number of positive-stranded RNA viruses. To determine if autophagy plays a role during FMDV replication, we analyzed the localization of hallmarks of the cellular autophagic pathway with different viral proteins. For these experiments a human cell line (MCF-10A), highly susceptible to FMDV infection, and a primary culture of bovine pharynx cells, which have been described as an important site of FMDV replication in susceptible animals, were utilized. At 5 hours post-infection (hpi), colocalization of LC3, a marker of autophagy, and the FMDV non-structural proteins 2B, 2C, and 3A, were observed. In addition, colocalization of LC3 and LAMP-1, characteristic of autophagosome formation, was also seen in FMDV infected cells. Rapamycin, a compound that stimulates autophagy, resulted in an increase in viral yield which was manifest to a greater degree in extracellular as opposed to intracellular virus. 3-methyladenine, an inhibitor of the autophagic pathway, decreased the yield of both intracellular and extracellular virus. Inhibition of expression of the autophagic complex genes, LC3 and APG12, using siRNA resulted in an inhibition of FMDV replication manifest in both intracellular and extracellular viral yields. These studies suggest that, although autophagy has both antiviral and antibacterial functions, it may play an important role during FMDV replication. Moreover, autophagy may represent a possible mechanism for the virus to maintain the carrier state and, under certain circumstances, possibly enable the non-lytic release of the virion from persistently infected cells.