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Title: FOOT-AND-MOUTH DISEASE VIRUS INTERNALIZES BY CLATHRIN-MEDIATED ENDOCYTOSIS

Author
item O'DONNELL, VIVIAN - UNIV CONNECTICUT
item Larocco, Michael
item Duque, Hernando
item Baxt, Barry

Submitted to: American Society for Virology Meeting
Publication Type: Abstract Only
Publication Acceptance Date: 5/1/2005
Publication Date: 6/18/2005
Citation: O'Donnell, V., Larocco, M.A., Duque, H., Baxt, B. 2005. Foot-and-Mouth Disease Virus Internalizes by Clathrin-mediated Endocytosis. American Society for Virology Meeting. p 144

Interpretive Summary:

Technical Abstract: Foot-and-mouth disease virus (FMDV) is the type species of the Aphthovirus genus, of the family Picornaviridae. It has been demonstrated that FMDV uses the a1phaVbeta1, alphaVbeta3, alphaVbeta6, and alphaVbeta8 integrins as receptors in vitro. The virus interacts with these receptors via a highly conserved arginine-glycine-aspartic acid (RGD) amino acid sequence motif located within the G-H loop of VP1. By using confocal microscopy, we analyzed the entry of two FMDV serotypes (types A and O) after interaction with the integrin receptors alphaVbeta3 and alphaVbeta6 at the cell surface. In cells which express both integrins, virus adsorbed to the cells at 4ºC appears to colocalize almost exclusively with the alphaVbeta6 integrin, while in cells expressing the alphaVbeta3 integrin, only the type A virus can be observed colocalizing with the receptor. FMDV capsid proteins were detected within 15 minutes after the temperature was shifted to 37C, in association with the integrin, in vesicular structures that were positive for a marker of clathrin-mediated endocytosis. In addition, in the presence of chlorpromazine, a compound that inhibits clathrin-mediated endocytosis, viral infection was markedly reduced. In contrast, virus did not colocalize with a marker for caveolae-mediated endocytosis. FMDV remained associated with the integrin until about 1 hour after the temperature shift, when viral proteins appeared around the perinuclear region of the cell. At the early phase of infection (15 min post-adsorption) FMD viral proteins were seen colocalizing with a marker for early endosomes, while no colocalization with late endosomal markers was observed. In the presence of monensin, a compound that raises the pH of endocytic vesicles and has been shown to inhibit FMDV replication, viral proteins were not released from the recycling endosome structures. These data indicate that FMDV utilizes the clathrin-mediated endocytosis pathway to infect the cells, and that viral replication begins due to acidification of endocytic vesicles causing the breakdown of the viral capsid structure and release of the genome.