title: Echovirus 7 entry into polarized caco-2 intestinal epithelial cells involves core components of the autophagy machinery.
abstract: Echovirus 7 enters polarized Caco-2 intestinal epithelial cells by a clathrin-mediated endocytic process and then moves through the endosomal system before releasing its genome into the cytoplasm. We examined the possible role in virus entry of core components of the autophagy machinery. We found that depletion of Beclin-1, Atg12, Atg14, Atg16, or LC3 with specific small interfering RNAs inhibited echovirus 7 infection upstream of uncoating but had little or no effect on virus attachment to the cell surface. These data indicate that multiple autophagy-related proteins are important for one or more events that occur after the virus has bound its receptor on the cell surface but before RNA is released from the virus capsid. Although we have not determined the mechanism by which each protein contributes to virus entry, we found that stable depletion of Atg16L1 interfered with virus internalization from the cell surface rather than with intracellular trafficking. Autophagy gene products may thus participate in the endocytic process that moves virus into polarized Caco-2 cells.
authors.affiliation: Division of Infectious Diseases, Children's Hospital of Philadelphia, Philadelphia, Pennsylvania, USA.
authors.forename: Chonsaeng
authors.initials: C
authors.lastname: Kim
authors.forename: Jeffrey M
authors.initials: JM
authors.lastname: Bergelson
mesh_terms: D033942:Adaptor Proteins, Vesicular Transport / Q000378:metabolism; D051017:Apoptosis Regulatory Proteins / Q000378:metabolism; D001343:Autophagy; D000071183:Autophagy-Related Proteins; D000071186:Beclin-1; D018938:Caco-2 Cells; D011992:Endosomes / Q000378:metabolism; D029822:Enterovirus B, Human / Q000502:physiology*; D006801:Humans; D007413:Intestinal Mucosa / Q000821:virology*; D008561:Membrane Fusion / Q000502:physiology*; D008565:Membrane Proteins / Q000378:metabolism; D019869:Phosphatidylinositol 3-Kinases / Q000378:metabolism
chemical_list: C539000:ATG14 protein, human; D033942:Adaptor Proteins, Vesicular Transport; D051017:Apoptosis Regulatory Proteins; D000071183:Autophagy-Related Proteins; C491997:BECN1 protein, human; D000071186:Beclin-1; D008565:Membrane Proteins; D019869:Phosphatidylinositol 3-Kinases