{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,5]],"date-time":"2026-10-05T20:32:41Z","timestamp":1791232361913,"version":"4.1.0"},"reference-count":25,"publisher":"American Society for Microbiology","issue":"19","license":[{"start":{"date-parts":[[2006,10,1]],"date-time":"2006-10-01T00:00:00Z","timestamp":1159660800000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/journals.asm.org\/non-commercial-tdm-license"}],"content-domain":{"domain":["journals.asm.org"],"crossmark-restriction":true},"short-container-title":["J Virol"],"published-print":{"date-parts":[[2006,10]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n          <jats:p>Invasion\nof glial cells by the human polyomavirus, JC virus (JCV), leads to a\nrapidly progressing and uniformly fatal demyelinating disease known as\nprogressive multifocal leukoencephalopathy. The endocytic trafficking\nsteps used by JCV to invade cells and initiate infection are not known.\nWe demonstrated that JCV infection was inhibited by dominant defective\nand constitutively active Rab5-GTPase mutants that acted at distinct\nsteps in endosomal sorting. We also found that labeled JCV colocalized\nwith labeled cholera toxin B and with caveolin-1 (cav-1) on early\nendosomes following internalization by clathrin-dependent endocytosis.\nJCV entry and infection were both inhibited by dominant defective\nmutants of eps15 and Rab5-GTPase. Expression of a dominant-negative\nscaffolding mutant of cav-1 did not inhibit entry or infection by JCV.\nA single-cell knockdown experiment using cav-1 shRNA did not inhibit\nJCV entry but interfered with a downstream trafficking event important\nfor infection. These data show that JCV enters cells by\nclathrin-dependent endocytosis, is transported immediately to early\nendosomes, and is then sorted to a caveolin-1-positive endosomal\ncompartment. This latter step is dependent on Rab5-GTPase, cholesterol,\ncaveolin-1, and pH. This is the first example of a ligand that enters\ncells by clathrin-dependent endocytosis and is then sorted from early\nendosomes to caveosomes, indicating that caveolae-derived vesicles play\na more important role than previously realized in sorting cargo from\nearly\nendosomes.<\/jats:p>","DOI":"10.1128\/jvi.01086-06","type":"journal-article","created":{"date-parts":[[2006,9,14]],"date-time":"2006-09-14T03:35:27Z","timestamp":1158204927000},"page":"9402-9413","update-policy":"https:\/\/doi.org\/10.1128\/asmj-crossmark-policy-page","source":"Crossref","is-referenced-by-count":95,"title":["Invasion of Host Cells by JC Virus Identifies a Novel Role for Caveolae in EndosomalSorting of Noncaveolar Ligands"],"prefix":"10.1128","volume":"80","author":[{"given":"W.","family":"Querbes","sequence":"first","affiliation":[{"name":"Graduate\rProgram in Pathobiology"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"B. A.","family":"O'Hara","sequence":"additional","affiliation":[{"name":"Department of Molecular\rBiology, Cell Biology, and Biochemistry, Brown\rUniversity, Providence, Rhode Island 02912"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"G.","family":"Williams","sequence":"additional","affiliation":[{"name":"Department of Molecular\rBiology, Cell Biology, and Biochemistry, Brown\rUniversity, Providence, Rhode Island 02912"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"W. J.","family":"Atwood","sequence":"additional","affiliation":[{"name":"Graduate\rProgram in Pathobiology"},{"name":"Department of Molecular\rBiology, Cell Biology, and Biochemistry, Brown\rUniversity, Providence, Rhode Island 02912"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"235","reference":[{"key":"e_1_3_2_2_2","doi-asserted-by":"publisher","DOI":"10.1128\/jvi.76.5.2340-2349.2002"},{"key":"e_1_3_2_3_2","doi-asserted-by":"publisher","DOI":"10.1083\/jcb.200109030"},{"key":"e_1_3_2_4_2","doi-asserted-by":"publisher","DOI":"10.1242\/jcs.112.9.1303"},{"key":"e_1_3_2_5_2","doi-asserted-by":"publisher","DOI":"10.1055\/s-2008-1040837"},{"key":"e_1_3_2_6_2","doi-asserted-by":"publisher","DOI":"10.1128\/JVI.77.6.3846-3850.2003"},{"key":"e_1_3_2_7_2","doi-asserted-by":"publisher","DOI":"10.1006\/excr.1998.4301"},{"key":"e_1_3_2_8_2","doi-asserted-by":"publisher","DOI":"10.1128\/JVI.78.21.11583-11590.2004"},{"key":"e_1_3_2_9_2","first-page":"1241","volume":"306","year":"2004","unstructured":"Fonseca-Elphick, G., W. Querbes, J. A. Jordan, G. V. Gee, S. Eash, K. Manley, A. Dugan, M. Stanifer, A. Bhatnagar, W. K. Kroeze, B. L. Roth, and W. J. Atwood. 2004 . The human polyomavirus, JCV, uses serotonin receptors to infect cells. Science306:1241-1420.","journal-title":"Science"},{"key":"e_1_3_2_10_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.bbamcr.2005.06.002"},{"key":"e_1_3_2_11_2","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa051782"},{"key":"e_1_3_2_12_2","doi-asserted-by":"publisher","DOI":"10.1002\/jmv.10450"},{"key":"e_1_3_2_13_2","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa051847"},{"key":"e_1_3_2_14_2","first-page":"9","volume":"165","year":"2001","unstructured":"Liu, C. K., and W. J. Atwood. 2001. Propagation and assay of the JC virus. Methods Mol. Biol.165:9-17.","journal-title":"Methods Mol. 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