{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,17]],"date-time":"2026-09-17T02:33:15Z","timestamp":1789612395320,"version":"build-2803163510"},"reference-count":33,"publisher":"Microbiology Society","issue":"11","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2013,11,1]]},"abstract":"<jats:p>Human cytomegalovirus (CMV) infects monocytes and other haematopoietic progenitor cells which then act as reservoirs for latency and virus dissemination. The chemokine CCL2 (monocyte chemotactic protein-1 or MCP-1) exhibits potent chemotactic activity for monocytes and is a likely target for CMV-induced immunomodulation. In this study, we demonstrate CMV modulates CCL2 expression in MRC-5 fibroblasts with multiplicity-dependent kinetics, where CCL2 is upregulated during early stage infection, followed by CCL2 inhibition at late stage infection. This CMV-induced CCL2 modulation was dependent upon virus replication, as UV-inactivated virus did not elicit any changes in CCL2 levels. Dual immunofluorescence staining showed CMV strains AD169, purified AD169, Merlin, FIX WT (FLAG-US28\/WT) and pUS28-deficient FIX (FIX-\u0394US28) all induced upregulation of CCL2 primarily within infected cells. Focal upregulation of CCL2 within FIX-\u0394US28-infected cells demonstrated intracellular CCL2 accumulation was independent of CCL2 sequestration by the CMV-encoded chemokine receptor US28. Infection with purified virus confirmed CMV-induced CCL2 upregulation was not due to any CCL2-inducing factors contained within non-purified virus stocks. The CMV-induced CCL2 expression kinetics occurred concurrently with modulation of the CCL2 transcriptional activators NF-\u03baB, interferon regulatory factor 3 and cytokine IFN-\u03b2, independent of virus strain, and with the establishment of viral replication compartments within infected cell nuclei. This is the first report to our knowledge to demonstrate CMV modulation of CCL2 expression within infected cells during viral replication. This immune modulation may facilitate virus dissemination, establishment of latency and pathogenesis of CMV-induced host disease.<\/jats:p>","DOI":"10.1099\/vir.0.052878-0","type":"journal-article","created":{"date-parts":[[2013,8,13]],"date-time":"2013-08-13T02:34:09Z","timestamp":1376361249000},"page":"2495-2503","source":"Crossref","is-referenced-by-count":35,"title":["Human cytomegalovirus directly modulates expression of chemokine CCL2 (MCP-1) during viral replication"],"prefix":"10.1099","volume":"94","author":[{"given":"Stuart T.","family":"Hamilton","sequence":"first","affiliation":[{"name":"School of Biotechnology and Biomolecular Sciences, University of New South Wales, Sydney, Australia"},{"name":"Virology Division, SEALS Microbiology, Prince of Wales Hospital, Sydney, Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gillian M.","family":"Scott","sequence":"additional","affiliation":[{"name":"School of Medical Sciences, University of New South Wales, Sydney, Australia"},{"name":"School of Biotechnology and Biomolecular Sciences, University of New South Wales, Sydney, Australia"},{"name":"Virology Division, SEALS Microbiology, Prince of Wales Hospital, Sydney, Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zin","family":"Naing","sequence":"additional","affiliation":[{"name":"School of Medical Sciences, University of New South Wales, Sydney, Australia"},{"name":"Virology Division, SEALS Microbiology, Prince of Wales Hospital, Sydney, Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"William D.","family":"Rawlinson","sequence":"additional","affiliation":[{"name":"School of Medical Sciences, University of New South Wales, Sydney, Australia"},{"name":"School of Biotechnology and Biomolecular Sciences, University of New South Wales, Sydney, Australia"},{"name":"Virology Division, SEALS Microbiology, Prince of Wales Hospital, Sydney, Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"345","reference":[{"key":"r1","doi-asserted-by":"publisher","DOI":"10.1128\/JVI.78.20.10995-11006.2004"},{"key":"r2","doi-asserted-by":"publisher","DOI":"10.1084\/jem.188.5.855"},{"key":"r3","first-page":"14E.3.1","article-title":"Human cytomegalovirus: propagation, quantification, and storage","volume-title":"Curr Protoc Microbiol","volume":"14","author":"Britt","year":"2010"},{"key":"r4","doi-asserted-by":"publisher","DOI":"10.1080\/jmf.12.3.159.164"},{"key":"r4a","doi-asserted-by":"publisher","DOI":"10.1080\/13550280152058799"},{"key":"r5","doi-asserted-by":"publisher","DOI":"10.1128\/JVI.76.10.4912-4918.2002"},{"key":"r6","doi-asserted-by":"publisher","DOI":"10.1016\/j.tcb.2003.10.009"},{"key":"r7","doi-asserted-by":"publisher","DOI":"10.1016\/j.immuni.2012.04.014"},{"key":"r8","doi-asserted-by":"publisher","DOI":"10.1128\/JVI.01748-09"},{"key":"r9","doi-asserted-by":"publisher","DOI":"10.1016\/j.placenta.2004.09.012"},{"key":"r10","doi-asserted-by":"publisher","DOI":"10.1161\/CIRCULATIONAHA.105.572396"},{"key":"r11","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0052899"},{"key":"r12","doi-asserted-by":"crossref","first-page":"4812","DOI":"10.4049\/jimmunol.1300089","article-title":"I\u03baB\u03b6 is a transcriptional key regulator of CCL2\/MCP-1","volume":"190","author":"Hildebrand","year":"2013","journal-title":"J Immunol"},{"key":"r13","doi-asserted-by":"crossref","first-page":"404","DOI":"10.1128\/JVI.73.1.404-410.1999","article-title":"Human cytomegalovirus inhibits transcription of the CC chemokine MCP-1 gene","volume":"73","author":"Hirsch","year":"1999","journal-title":"J Virol"},{"key":"r14","doi-asserted-by":"publisher","DOI":"10.1093\/infdis\/jir121"},{"key":"r15","doi-asserted-by":"publisher","DOI":"10.1128\/JVI.00060-06"},{"key":"r16","doi-asserted-by":"publisher","DOI":"10.1186\/1471-2105-8-131"},{"key":"r17","doi-asserted-by":"publisher","DOI":"10.1007\/s00795-003-0223-2"},{"key":"r18","doi-asserted-by":"crossref","first-page":"8008","DOI":"10.4049\/jimmunol.177.11.8008","article-title":"The IFN-independent response to virus particle entry provides a first line of antiviral defense that is independent of TLRs and retinoic acid-inducible gene I","volume":"177","author":"Paladino","year":"2006","journal-title":"J Immunol"},{"key":"r19","doi-asserted-by":"publisher","DOI":"10.1093\/nar\/29.9.e45"},{"key":"r20","doi-asserted-by":"publisher","DOI":"10.1038\/nri1604"},{"key":"r21","doi-asserted-by":"publisher","DOI":"10.1093\/nar\/gkp045"},{"key":"r22","doi-asserted-by":"publisher","DOI":"10.1093\/infdis\/jis186"},{"key":"r23","doi-asserted-by":"publisher","DOI":"10.1172\/JCI42955"},{"key":"r24","doi-asserted-by":"publisher","DOI":"10.1086\/508173"},{"key":"r25","doi-asserted-by":"crossref","first-page":"6577","DOI":"10.4049\/jimmunol.180.10.6577","article-title":"Human cytomegalovirus latent infection of myeloid cells directs monocyte migration by up-regulating monocyte chemotactic protein-1","volume":"180","author":"Stern","year":"2008","journal-title":"J Immunol"},{"key":"r26","doi-asserted-by":"publisher","DOI":"10.1099\/vir.0.83226-0"},{"key":"r27","doi-asserted-by":"publisher","DOI":"10.1086\/655472"},{"key":"r28","doi-asserted-by":"crossref","first-page":"research0034.1","DOI":"10.1186\/gb-2002-3-7-research0034","article-title":"Accurate normalization of real-time quantitative RT-PCR data by geometric averaging of multiple internal control genes","volume":"3","author":"Vandesompele","year":"2002","journal-title":"Genome Biol"},{"key":"r29","doi-asserted-by":"publisher","DOI":"10.1128\/JVI.06338-11"},{"key":"r30","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.250477397"},{"key":"r31","doi-asserted-by":"crossref","first-page":"5391","DOI":"10.1128\/JVI.69.9.5391-5400.1995","article-title":"Human cytomegalovirus upregulates NF-\u03baB activity by transactivating the NF-\u03baB p105\/p50 and p65 promoters","volume":"69","author":"Yurochko","year":"1995","journal-title":"J Virol"},{"key":"r32","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.94.25.13985"}],"container-title":["Journal of General Virology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.microbiologyresearch.org\/content\/journal\/jgv\/10.1099\/vir.0.052878-0?crawler=true","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2020,10,27]],"date-time":"2020-10-27T00:17:52Z","timestamp":1603757872000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.microbiologyresearch.org\/content\/journal\/jgv\/10.1099\/vir.0.052878-0"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2013,11,1]]},"references-count":33,"journal-issue":{"issue":"11","published-print":{"date-parts":[[2013,11,1]]}},"URL":"https:\/\/doi.org\/10.1099\/vir.0.052878-0","relation":{},"ISSN":["0022-1317","1465-2099"],"issn-type":[{"value":"0022-1317","type":"print"},{"value":"1465-2099","type":"electronic"}],"subject":[],"published":{"date-parts":[[2013,11,1]]}}}