{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,12]],"date-time":"2026-06-12T21:51:34Z","timestamp":1781301094304,"version":"3.54.1"},"reference-count":64,"publisher":"American Society for Microbiology","issue":"17","license":[{"start":{"date-parts":[[2016,9,1]],"date-time":"2016-09-01T00:00:00Z","timestamp":1472688000000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/journals.asm.org\/non-commercial-tdm-license"}],"funder":[{"DOI":"10.13039\/501100000925","name":"Department of Health | National Health and Medical Research Council","doi-asserted-by":"publisher","award":["1083307"],"award-info":[{"award-number":["1083307"]}],"id":[{"id":"10.13039\/501100000925","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100000925","name":"Department of Health | National Health and Medical Research Council","doi-asserted-by":"publisher","award":["1027545"],"award-info":[{"award-number":["1027545"]}],"id":[{"id":"10.13039\/501100000925","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["journals.asm.org"],"crossmark-restriction":true},"short-container-title":["J Virol"],"published-print":{"date-parts":[[2016,9]]},"abstract":"<jats:title>ABSTRACT<\/jats:title><jats:p>It is well established that glycosaminoglycans (GAGs) function as attachment factors for human metapneumovirus (HMPV), concentrating virions at the cell surface to promote interaction with other receptors for virus entry and infection. There is increasing evidence to suggest that multiple receptors may exhibit the capacity to promote infectious entry of HMPV into host cells; however, definitive identification of specific transmembrane receptors for HMPV attachment and entry is complicated by the widespread expression of cell surface GAGs. pgsA745 Chinese hamster ovary (CHO) cells are deficient in the expression of cell surface GAGs and resistant to HMPV infection. Here, we demonstrate that the expression of the Ca<jats:sup>2+<\/jats:sup>-dependent C-type lectin receptor (CLR) DC-SIGN (CD209L) or L-SIGN (CD209L) rendered pgsA745 cells permissive to HMPV infection. Unlike infection of parental CHO cells, HMPV infection of pgsA745 cells expressing DC-SIGN or L-SIGN was dynamin dependent and inhibited by mannan but not by pretreatment with bacterial heparinase. Parental CHO cells expressing DC-SIGN\/L-SIGN also showed enhanced susceptibility to dynamin-dependent HMPV infection, confirming that CLRs can promote HMPV infection in the presence or absence of GAGs. Comparison of pgsA745 cells expressing wild-type and endocytosis-defective mutants of DC-SIGN\/L-SIGN indicated that the endocytic function of CLRs was not essential but could contribute to HMPV infection of GAG-deficient cells. Together, these studies confirm a role for CLRs as attachment factors and entry receptors for HMPV infection. Moreover, they define an experimental system that can be exploited to identify transmembrane receptors and entry pathways where permissivity to HMPV infection can be rescued following the expression of a single cell surface receptor.<\/jats:p><jats:p><jats:bold>IMPORTANCE<\/jats:bold>On the surface of CHO cells, glycosaminoglycans (GAGs) function as the major attachment factor for human metapneumoviruses (HMPV), promoting dynamin-independent infection. Consistent with this, GAG-deficient pgaA745 CHO cells are resistant to HMPV. However, expression of DC-SIGN or L-SIGN rendered pgsA745 cells permissive to dynamin-dependent infection by HMPV, although the endocytic function of DC-SIGN\/L-SIGN was not essential for, but could contribute to, enhanced infection. These studies provide direct evidence implicating DC-SIGN\/L-SIGN as an alternate attachment factor for HMPV attachment, promoting dynamin-dependent infection via other unknown receptors in the absence of GAGs. Moreover, we describe a unique experimental system for the assessment of putative attachment and entry receptors for HMPV.<\/jats:p>","DOI":"10.1128\/jvi.00537-16","type":"journal-article","created":{"date-parts":[[2016,6,24]],"date-time":"2016-06-24T05:29:03Z","timestamp":1466746143000},"page":"7848-7863","update-policy":"https:\/\/doi.org\/10.1128\/asmj-crossmark-policy-page","source":"Crossref","is-referenced-by-count":17,"title":["DC-SIGN and L-SIGN Are Attachment Factors That Promote Infection of Target Cells by Human Metapneumovirus in the Presence or Absence of Cellular Glycosaminoglycans"],"prefix":"10.1128","volume":"90","author":[{"given":"Leah","family":"Gillespie","sequence":"first","affiliation":[{"name":"Department of Microbiology and Immunology, University of Melbourne at the Peter Doherty Institute for Infection and Immunity, Melbourne, Victoria, Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kathleen","family":"Gerstenberg","sequence":"additional","affiliation":[{"name":"Department of Microbiology and Immunology, University of Melbourne at the Peter Doherty Institute for Infection and Immunity, Melbourne, Victoria, Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fernanda","family":"Ana-Sosa-Batiz","sequence":"additional","affiliation":[{"name":"Department of Microbiology and Immunology, University of Melbourne at the Peter Doherty Institute for Infection and Immunity, Melbourne, Victoria, Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Matthew S.","family":"Parsons","sequence":"additional","affiliation":[{"name":"Department of Microbiology and Immunology, University of Melbourne at the Peter Doherty Institute for Infection and Immunity, Melbourne, Victoria, Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rubaiyea","family":"Farrukee","sequence":"additional","affiliation":[{"name":"WHO Collaborating Centre for Reference and Research on Influenza, Victorian Infectious Diseases Reference Laboratory at the Peter Doherty Institute for Infection and Immunity, Melbourne, Victoria, Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mark","family":"Krabbe","sequence":"additional","affiliation":[{"name":"Department of Microbiology and Immunology, University of Melbourne at the Peter Doherty Institute for Infection and Immunity, Melbourne, Victoria, Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kirsten","family":"Spann","sequence":"additional","affiliation":[{"name":"School of Biomedical Science, Faculty of Health, Queensland University of Technology, Brisbane, Queensland, Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Andrew G.","family":"Brooks","sequence":"additional","affiliation":[{"name":"Department of Microbiology and Immunology, University of Melbourne at the Peter Doherty Institute for Infection and Immunity, Melbourne, Victoria, Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sarah L.","family":"Londrigan","sequence":"additional","affiliation":[{"name":"Department of Microbiology and Immunology, University of Melbourne at the Peter Doherty Institute for Infection and Immunity, Melbourne, Victoria, Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Patrick C.","family":"Reading","sequence":"additional","affiliation":[{"name":"Department of Microbiology and Immunology, University of Melbourne at the Peter Doherty Institute for Infection and Immunity, Melbourne, Victoria, Australia"},{"name":"WHO Collaborating Centre for Reference and Research on Influenza, Victorian Infectious Diseases Reference Laboratory at the Peter Doherty Institute for Infection and Immunity, Melbourne, Victoria, Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"235","reference":[{"key":"e_1_3_2_2_2","doi-asserted-by":"publisher","DOI":"10.1055\/s-0031-1283284"},{"key":"e_1_3_2_3_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0002-9440(10)63750-9"},{"key":"e_1_3_2_4_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.antiviral.2004.12.009"},{"key":"e_1_3_2_5_2","doi-asserted-by":"publisher","DOI":"10.1165\/rcmb.2013-0414OC"},{"key":"e_1_3_2_6_2","doi-asserted-by":"publisher","DOI":"10.1165\/rcmb.2005-0287OC"},{"key":"e_1_3_2_7_2","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.1002589"},{"key":"e_1_3_2_8_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.virol.2008.11.043"},{"key":"e_1_3_2_9_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.virol.2006.08.004"},{"key":"e_1_3_2_10_2","doi-asserted-by":"publisher","DOI":"10.3390\/v5010192"},{"key":"e_1_3_2_11_2","doi-asserted-by":"publisher","DOI":"10.1128\/JVI.00128-07"},{"key":"e_1_3_2_12_2","doi-asserted-by":"publisher","DOI":"10.1128\/JVI.78.23.12877-12887.2004"},{"key":"e_1_3_2_13_2","doi-asserted-by":"publisher","DOI":"10.1128\/JVI.79.19.12608-12613.2005"},{"key":"e_1_3_2_14_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.0801433106"},{"key":"e_1_3_2_15_2","doi-asserted-by":"publisher","DOI":"10.1128\/JVI.01133-12"},{"key":"e_1_3_2_16_2","doi-asserted-by":"publisher","DOI":"10.1371\/journal.ppat.1005303"},{"key":"e_1_3_2_17_2","doi-asserted-by":"publisher","DOI":"10.1128\/JVI.03491-13"},{"key":"e_1_3_2_18_2","doi-asserted-by":"publisher","DOI":"10.1128\/JVI.06706-11"},{"key":"e_1_3_2_19_2","first-page":"189","article-title":"Local increase of beta 1-integrin expression in cocultures of immortalized hepatocytes and sinusoidal endothelial cells","volume":"65","author":"Henning W","year":"1994","unstructured":"Henning W, Bohn W, Nebe B, Knopp A, Rychly J, Strauss M. 1994. Local increase of beta 1-integrin expression in cocultures of immortalized hepatocytes and sinusoidal endothelial cells. Eur J Cell Biol 65:189\u2013199.","journal-title":"Eur J Cell Biol"},{"key":"e_1_3_2_20_2","doi-asserted-by":"publisher","DOI":"10.1007\/978-1-4614-7651-1_1"},{"key":"e_1_3_2_21_2","doi-asserted-by":"publisher","DOI":"10.3390\/v4123785"},{"key":"e_1_3_2_22_2","doi-asserted-by":"publisher","DOI":"10.1128\/JVI.01208-08"},{"key":"e_1_3_2_23_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.antiviral.2004.02.006"},{"key":"e_1_3_2_24_2","doi-asserted-by":"publisher","DOI":"10.1128\/JVI.01381-08"},{"key":"e_1_3_2_25_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.82.10.3197"},{"key":"e_1_3_2_26_2","doi-asserted-by":"publisher","DOI":"10.1189\/jlb.1011492"},{"key":"e_1_3_2_27_2","doi-asserted-by":"publisher","DOI":"10.1128\/JVI.03261-13"},{"key":"e_1_3_2_28_2","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.273.32.20189"},{"key":"e_1_3_2_29_2","doi-asserted-by":"publisher","DOI":"10.1083\/jcb.85.1.60"},{"key":"e_1_3_2_30_2","doi-asserted-by":"publisher","DOI":"10.1086\/315134"},{"key":"e_1_3_2_31_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.87.12.4485"},{"key":"e_1_3_2_32_2","doi-asserted-by":"publisher","DOI":"10.1128\/JVI.01705-10"},{"key":"e_1_3_2_33_2","doi-asserted-by":"publisher","DOI":"10.1038\/srep19428"},{"key":"e_1_3_2_34_2","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M109.068353"},{"key":"e_1_3_2_35_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0021-9258(18)47838-6"},{"key":"e_1_3_2_36_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0021-9258(18)80078-3"},{"key":"e_1_3_2_37_2","doi-asserted-by":"publisher","DOI":"10.1093\/glycob\/cwn080"},{"key":"e_1_3_2_38_2","doi-asserted-by":"publisher","DOI":"10.3967\/0895-3988.2011.01.011"},{"key":"e_1_3_2_39_2","doi-asserted-by":"publisher","DOI":"10.1006\/viro.2000.0293"},{"key":"e_1_3_2_40_2","doi-asserted-by":"publisher","DOI":"10.1128\/JVI.00986-09"},{"key":"e_1_3_2_41_2","doi-asserted-by":"publisher","DOI":"10.1099\/0022-1317-81-11-2715"},{"key":"e_1_3_2_42_2","doi-asserted-by":"publisher","DOI":"10.1128\/JVI.06096-11"},{"key":"e_1_3_2_43_2","doi-asserted-by":"publisher","DOI":"10.1146\/annurev.biochem.78.081307.110540"},{"key":"e_1_3_2_44_2","doi-asserted-by":"publisher","DOI":"10.1007\/82_2014_393"},{"key":"e_1_3_2_45_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.75.7.3327"},{"key":"e_1_3_2_46_2","doi-asserted-by":"publisher","DOI":"10.1128\/JVI.00472-08"},{"key":"e_1_3_2_47_2","doi-asserted-by":"publisher","DOI":"10.1128\/JVI.01287-06"},{"key":"e_1_3_2_48_2","doi-asserted-by":"publisher","DOI":"10.1128\/JVI.05485-11"},{"key":"e_1_3_2_49_2","doi-asserted-by":"publisher","DOI":"10.1099\/0022-1317-75-10-2595"},{"key":"e_1_3_2_50_2","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.168.5.2118"},{"key":"e_1_3_2_51_2","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M504337200"},{"key":"e_1_3_2_52_2","doi-asserted-by":"publisher","DOI":"10.3390\/v6031294"},{"key":"e_1_3_2_53_2","doi-asserted-by":"publisher","DOI":"10.1128\/JVI.02780-06"},{"key":"e_1_3_2_54_2","doi-asserted-by":"publisher","DOI":"10.1371\/journal.ppat.1003309"},{"key":"e_1_3_2_55_2","doi-asserted-by":"publisher","DOI":"10.1128\/JVI.06274-11"},{"key":"e_1_3_2_56_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.micinf.2004.05.002"},{"key":"e_1_3_2_57_2","doi-asserted-by":"publisher","DOI":"10.1086\/520607"},{"key":"e_1_3_2_58_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.chom.2011.06.007"},{"key":"e_1_3_2_59_2","doi-asserted-by":"publisher","DOI":"10.1007\/s00109-008-0350-2"},{"key":"e_1_3_2_60_2","doi-asserted-by":"publisher","DOI":"10.3109\/08830185.2013.834897"},{"key":"e_1_3_2_61_2","doi-asserted-by":"publisher","DOI":"10.1128\/JVI.80.7.3477-3486.2006"},{"key":"e_1_3_2_62_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.chom.2014.06.008"},{"key":"e_1_3_2_63_2","doi-asserted-by":"crossref","first-page":"445","DOI":"10.1189\/jlb.71.3.445","article-title":"Constitutive and induced expression of DC-SIGN on dendritic cell and macrophage subpopulations in situ and in vitro","volume":"71","author":"Soilleux EJ","year":"2002","unstructured":"Soilleux EJ, Morris LS, Leslie G, Chehimi J, Luo Q, Levroney E, Trowsdale J, Montaner LJ, Doms RW, Weissman D, Coleman N, Lee B. 2002. Constitutive and induced expression of DC-SIGN on dendritic cell and macrophage subpopulations in situ and in vitro. J Leukoc Biol 71:445\u2013457.","journal-title":"J Leukoc Biol"},{"key":"e_1_3_2_64_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0002-9440(10)63717-0"},{"key":"e_1_3_2_65_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.0403812101"}],"container-title":["Journal of Virology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/journals.asm.org\/doi\/pdf\/10.1128\/JVI.00537-16","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/journals.asm.org\/doi\/pdf\/10.1128\/JVI.00537-16","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2024,6,17]],"date-time":"2024-06-17T21:32:35Z","timestamp":1718659955000},"score":1,"resource":{"primary":{"URL":"https:\/\/journals.asm.org\/doi\/10.1128\/JVI.00537-16"}},"subtitle":[],"editor":[{"given":"T. S.","family":"Dermody","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"editor"}]}],"short-title":[],"issued":{"date-parts":[[2016,9]]},"references-count":64,"journal-issue":{"issue":"17","published-print":{"date-parts":[[2016,9]]}},"alternative-id":["10.1128\/JVI.00537-16"],"URL":"https:\/\/doi.org\/10.1128\/jvi.00537-16","relation":{},"ISSN":["0022-538X","1098-5514"],"issn-type":[{"value":"0022-538X","type":"print"},{"value":"1098-5514","type":"electronic"}],"subject":[],"published":{"date-parts":[[2016,9]]},"assertion":[{"value":"2016-03-21","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2016-06-15","order":1,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2016-08-12","order":2,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}