{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,5]],"date-time":"2026-10-05T16:34:31Z","timestamp":1791218071807,"version":"4.1.0"},"reference-count":71,"publisher":"American Society for Microbiology","issue":"3","license":[{"start":{"date-parts":[[2008,2,1]],"date-time":"2008-02-01T00:00:00Z","timestamp":1201824000000},"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":[[2008,2]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n          <jats:p>\n            Recently, Misinzo et al. (G. Misinzo, P. Meerts, M. Bublot, J. Mast, H. M. Weingartl, and H. J. Nauwynck, J. Gen. Virol.\n            <jats:bold>86<\/jats:bold>\n            :2057-2068, 2005) reported that inhibiting endosome-lysosome system acidification reduced porcine circovirus 2 (PCV2) infection of monocytic 3D4\/31 cells. The present study examined the effect of inhibiting endosome-lysosome system acidification in epithelial cells, since epithelial cells support PCV2 infection in vivo and are used in culturing PCV2 in vitro. Ammonium chloride (NH\n            <jats:sub>4<\/jats:sub>\n            Cl), chloroquine diphosphate (CQ), and monensin were used to inhibit endosome-lysosome system acidification. NH\n            <jats:sub>4<\/jats:sub>\n            Cl, CQ, or monensin increased PCV2 (Stoon-1010) infection by 726% \u00b1 110%, 1,212% \u00b1 34%, and 1,100% \u00b1 179%, respectively, in porcine kidney (PK-15) cells; by 128% \u00b1 7%, 158% \u00b1 3%, and 142% \u00b1 11% in swine kidney cells; by 160% \u00b1 28%, 446% \u00b1 50%, and 162% \u00b1 56% in swine testicle (ST) cells; and by 313% \u00b1 25%, 611% \u00b1 86%, and 352% \u00b1 44% in primary kidney epithelial cells. Similarly, increased PCV2 infection was observed with six other PCV2 strains in PK-15 cells treated with endosome-lysosome system acidification inhibitors. The mechanism behind increased PCV2 infection was further investigated in PK-15 cells using CQ. PCV2 infection of PK-15 cells was increased only when CQ was added early during PCV2 infection. CQ did not affect PCV2 virus-like particle (VLP) attachment to PK-15 cells but increased the disassembly of internalized PCV2 VLPs. In untreated PK-15 cells, internalized PCV2 VLPs localized within the endosome-lysosome system. PCV2 infection of untreated 3D4\/31 and PK-15 cells and CQ-treated PK-15 cells was blocked by a serine protease inhibitor [4-(2-aminoethyl) benzenesulfonyl fluoride hydrochloride] but not by aspartyl protease (pepstatin A), cysteine protease (E-64), and metalloprotease (phosphoramidon) inhibitors. These results suggest that serine protease-mediated PCV2 disassembly is enhanced in porcine epithelial cells but inhibited in monocytic cells after inhibition of endosome-lysosome system acidification.\n          <\/jats:p>","DOI":"10.1128\/jvi.01229-07","type":"journal-article","created":{"date-parts":[[2007,11,22]],"date-time":"2007-11-22T01:53:55Z","timestamp":1195696435000},"page":"1128-1135","update-policy":"https:\/\/doi.org\/10.1128\/asmj-crossmark-policy-page","source":"Crossref","is-referenced-by-count":104,"title":["Inhibition of Endosome-Lysosome System Acidification Enhances Porcine Circovirus 2 Infection of Porcine Epithelial Cells"],"prefix":"10.1128","volume":"82","author":[{"given":"Gerald","family":"Misinzo","sequence":"first","affiliation":[{"name":"Laboratory of Virology, Faculty of Veterinary Medicine, Ghent University, Salisburylaan 133, 9820 Merelbeke, Belgium"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Peter L.","family":"Delputte","sequence":"additional","affiliation":[{"name":"Laboratory of Virology, Faculty of Veterinary Medicine, Ghent University, Salisburylaan 133, 9820 Merelbeke, Belgium"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hans J.","family":"Nauwynck","sequence":"additional","affiliation":[{"name":"Laboratory of Virology, Faculty of Veterinary Medicine, Ghent University, Salisburylaan 133, 9820 Merelbeke, Belgium"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"235","reference":[{"key":"e_1_3_2_2_2","doi-asserted-by":"publisher","DOI":"10.1111\/j.1600-0773.1988.tb01895.x"},{"key":"e_1_3_2_3_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0378-1135(99)00004-8"},{"key":"e_1_3_2_4_2","doi-asserted-by":"publisher","DOI":"10.1007\/s007050070031"},{"key":"e_1_3_2_5_2","doi-asserted-by":"publisher","DOI":"10.1016\/0076-6879(94)44003-4"},{"key":"e_1_3_2_6_2","doi-asserted-by":"publisher","DOI":"10.1097\/00001756-199806220-00033"},{"key":"e_1_3_2_7_2","doi-asserted-by":"publisher","DOI":"10.1128\/CMR.16.2.175-188.2003"},{"key":"e_1_3_2_8_2","doi-asserted-by":"publisher","DOI":"10.1126\/science.6297010"},{"key":"e_1_3_2_9_2","doi-asserted-by":"publisher","DOI":"10.1016\/0042-6822(84)90208-3"},{"key":"e_1_3_2_10_2","doi-asserted-by":"publisher","DOI":"10.1006\/viro.2002.1733"},{"key":"e_1_3_2_11_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0378-5173(01)00623-8"},{"key":"e_1_3_2_12_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.78.11.6922"},{"key":"e_1_3_2_13_2","doi-asserted-by":"publisher","DOI":"10.1016\/0006-2952(74)90174-9"},{"key":"e_1_3_2_14_2","first-page":"44","volume":"39","year":"1998","unstructured":"Ellis, J., L. 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