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

Author
item O'DONNELL, VIVIAN - UNIV. OF CONNECTICUT
item PACHECO-TOBIN, JUAN - OAK RIDGE INS SCIENCE, TN
item Larocco, Michael
item JACKSON, WILLIAM - STANFORD UNIV., CA
item Baxt, Barry

Submitted to: Keystone Symposia
Publication Type: Abstract Only
Publication Acceptance Date: 2/2/2006
Publication Date: 2/24/2006
Citation: O'Donnell, V.K., Pacheco-Tobin, J., Larocco, M.A., Jackson, W., Baxt, B. 2006. Foot-and-mouth disease virus utilizes an autophagic pathway during viral replication. Keystone Symposia. 2006. P. 50

Interpretive Summary:

Technical Abstract: Foot-and-mouth disease virus (FMDV) is the type species of the Aphthovirus genus, of the family Picornaviridae. Infection with postive-strand RNA viruses results in the rearrangement of intracellular membranes into viral replication complexes which are the sites of viral RNA replication. Cellular autophagy has been proposed to be a mechanism of replication complex 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 our 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 the FMDV non-structural proteins 2B, 2C and 3A, and LC3, a marker of autophagy were observed. In addition, colocalization of LC3 and LAMP-1, characteristics 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 intracelllular virus. 3-methyladenine, an inhibitor of the autophagic pathway, decreased the yeild of both intracellular and extracellular virus. 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 viron from persistently infected cells.