{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,6]],"date-time":"2026-10-06T08:35:09Z","timestamp":1791275709024,"version":"4.1.0"},"reference-count":41,"publisher":"National Academy of Sciences","issue":"52","content-domain":{"domain":["www.pnas.org"],"crossmark-restriction":true},"short-container-title":["Proc. Natl. Acad. Sci. U.S.A."],"published-print":{"date-parts":[[2009,12,29]]},"abstract":"<jats:p>Human cytomegalovirus (HCMV) rapidly induces a mobile and functionally unique proinflammatory monocyte following infection that is proposed to mediate viral spread. The cellular pathways used by HCMV to initiate these biological changes remain unknown. Here, we document the expression of the epidermal growth factor receptor (EGFR) on the surface of human peripheral blood monocytes but not on other blood leukocyte populations. Inhibition of EGFR signaling abrogated viral entry into monocytes, indicating that EGFR can serve as a cellular tropism receptor. Moreover, HCMV-activated EGFR was required for the induction of monocyte motility and transendothelial migration, two biological events required for monocyte extravasation into peripheral tissue, and thus viral spread. Transcriptome analysis revealed that HCMV-mediated EGFR signaling up-regulated neural Wiskott\u2013Aldrich syndrome protein (N-WASP), an actin nucleator whose expression and function are normally limited in leukocytes. Knockdown of N-WASP expression blocked HCMV-induced but not phorbol 12-myristate 13-acetate (PMA)-induced monocyte motility, suggesting that a switch to and\/or the distinct use of a new actin nucleator controlling motility occurs during HCMV infection of monocytes. Together, these data provide evidence that EGFR plays an essential role in the immunopathobiology of HCMV by mediating viral entry into monocytes and stimulating the aberrant biological activity that promotes hematogenous dissemination.<\/jats:p>","DOI":"10.1073\/pnas.0908787106","type":"journal-article","created":{"date-parts":[[2009,12,11]],"date-time":"2009-12-11T21:31:03Z","timestamp":1260567063000},"page":"22369-22374","update-policy":"https:\/\/doi.org\/10.1073\/pnas.cm10313","source":"Crossref","is-referenced-by-count":184,"title":["Activation of EGFR on monocytes is required for human cytomegalovirus entry and mediates cellular motility"],"prefix":"10.1073","volume":"106","author":[{"given":"Gary","family":"Chan","sequence":"first","affiliation":[{"name":"Department of Microbiology and Immunology, Center for Molecular and Tumor Virology, and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maciej T.","family":"Nogalski","sequence":"additional","affiliation":[{"name":"Department of Microbiology and Immunology, Center for Molecular and Tumor Virology, and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Andrew D.","family":"Yurochko","sequence":"additional","affiliation":[{"name":"Department of Microbiology and Immunology, Center for Molecular and Tumor Virology, and"},{"name":"Feist\u2013Weiller Cancer Center, Louisiana State University Health Sciences Center, Shreveport, LA 71130-3932"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"341","published-online":{"date-parts":[[2009,12,29]]},"reference":[{"key":"e_1_3_3_1_2","doi-asserted-by":"publisher","DOI":"10.1093\/infdis\/160.5.741"},{"key":"e_1_3_3_2_2","doi-asserted-by":"publisher","DOI":"10.1159\/000150502"},{"key":"e_1_3_3_3_2","doi-asserted-by":"publisher","DOI":"10.1189\/jlb.1203621"},{"key":"e_1_3_3_4_2","doi-asserted-by":"publisher","DOI":"10.1128\/JVI.78.9.4444-4453.2004"},{"key":"e_1_3_3_5_2","doi-asserted-by":"publisher","DOI":"10.1128\/JVI.02839-06"},{"key":"e_1_3_3_6_2","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.181.1.698"},{"key":"e_1_3_3_7_2","doi-asserted-by":"crossref","first-page":"4806","DOI":"10.4049\/jimmunol.162.8.4806","article-title":"Human cytomegalovirus binding to human monocytes induces immunoregulatory gene expression","volume":"162","author":"Yurochko AD","year":"1999","unstructured":"AD Yurochko, ES Huang, Human cytomegalovirus binding to human monocytes induces immunoregulatory gene expression. J Immunol 162, 4806\u20134816 (1999).","journal-title":"J Immunol"},{"key":"e_1_3_3_8_2","doi-asserted-by":"publisher","DOI":"10.1038\/nature01818"},{"key":"e_1_3_3_9_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.0800037105"},{"key":"e_1_3_3_10_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.placenta.2005.03.003"},{"key":"e_1_3_3_11_2","doi-asserted-by":"publisher","DOI":"10.1128\/JVI.02748-06"},{"key":"e_1_3_3_12_2","doi-asserted-by":"publisher","DOI":"10.1128\/JVI.00169-07"},{"key":"e_1_3_3_13_2","doi-asserted-by":"publisher","DOI":"10.1038\/nature07209"},{"key":"e_1_3_3_14_2","first-page":"4726","article-title":"Expression of epidermal growth factor receptor in human cultured cells and tissues: Relationship to cell lineage and stage of differentiation","volume":"46","author":"Real FX","year":"1986","unstructured":"FX Real, et al., Expression of epidermal growth factor receptor in human cultured cells and tissues: Relationship to cell lineage and stage of differentiation. Cancer Res 46, 4726\u20134731 (1986).","journal-title":"Cancer Res"},{"key":"e_1_3_3_15_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.atherosclerosis.2005.06.038"},{"key":"e_1_3_3_16_2","doi-asserted-by":"publisher","DOI":"10.1046\/j.1462-5822.2002.00185.x"},{"key":"e_1_3_3_17_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.190351397"},{"key":"e_1_3_3_18_2","doi-asserted-by":"crossref","first-page":"1026","DOI":"10.4049\/jimmunol.161.2.1026","article-title":"Monocytes from Wiskott-Aldrich patients display reduced chemotaxis and lack of cell polarization in response to monocyte chemoattractant protein-1 and formyl-methionyl-leucyl-phenylalanine","volume":"161","author":"Badolato R","year":"1998","unstructured":"R Badolato, et al., Monocytes from Wiskott-Aldrich patients display reduced chemotaxis and lack of cell polarization in response to monocyte chemoattractant protein-1 and formyl-methionyl-leucyl-phenylalanine. J Immunol 161, 1026\u20131033 (1998).","journal-title":"J Immunol"},{"key":"e_1_3_3_19_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0021-9258(20)80533-X"},{"key":"e_1_3_3_20_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.tcb.2003.10.009"},{"key":"e_1_3_3_21_2","first-page":"2012","article-title":"Decreased arachidonic acid release in peripheral blood monocytes of patients with systemic lupus erythematosus","volume":"28","author":"Sipka S","year":"2001","unstructured":"S Sipka, et al., Decreased arachidonic acid release in peripheral blood monocytes of patients with systemic lupus erythematosus. J Rheumatol 28, 2012\u20132017 (2001).","journal-title":"J Rheumatol"},{"key":"e_1_3_3_22_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.0406821101"},{"key":"e_1_3_3_23_2","doi-asserted-by":"publisher","DOI":"10.1038\/nm1236"},{"key":"e_1_3_3_24_2","doi-asserted-by":"publisher","DOI":"10.1038\/sj.embor.7400234"},{"key":"e_1_3_3_25_2","doi-asserted-by":"publisher","DOI":"10.1099\/0022-1317-80-11-2867"},{"key":"e_1_3_3_26_2","doi-asserted-by":"publisher","DOI":"10.1128\/JVI.01016-06"},{"key":"e_1_3_3_27_2","doi-asserted-by":"publisher","DOI":"10.1111\/j.1549-8719.2001.tb00168.x"},{"key":"e_1_3_3_28_2","doi-asserted-by":"publisher","DOI":"10.1242\/jcs.02444"},{"key":"e_1_3_3_29_2","doi-asserted-by":"publisher","DOI":"10.1242\/jcs.005942"},{"key":"e_1_3_3_30_2","doi-asserted-by":"publisher","DOI":"10.1091\/mbc.e03-08-0609"},{"key":"e_1_3_3_31_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2007.02.028"},{"key":"e_1_3_3_32_2","doi-asserted-by":"publisher","DOI":"10.1093\/infdis\/173.5.1072"},{"key":"e_1_3_3_33_2","doi-asserted-by":"publisher","DOI":"10.1159\/000150501"},{"key":"e_1_3_3_34_2","doi-asserted-by":"publisher","DOI":"10.1007\/s11060-007-9423-2"},{"key":"e_1_3_3_35_2","doi-asserted-by":"publisher","DOI":"10.1099\/vir.0.79888-0"},{"key":"e_1_3_3_36_2","doi-asserted-by":"publisher","DOI":"10.1128\/jvi.70.1.78-83.1996"},{"key":"e_1_3_3_37_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.2136652100"},{"key":"e_1_3_3_38_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.0804365105"},{"key":"e_1_3_3_39_2","doi-asserted-by":"publisher","DOI":"10.1091\/mbc.e06-04-0261"},{"key":"e_1_3_3_40_2","doi-asserted-by":"crossref","first-page":"593","DOI":"10.1189\/jlb.68.5.593","article-title":"Cellular signaling in macrophage migration and chemotaxis","volume":"68","author":"Jones GE","year":"2000","unstructured":"GE Jones, Cellular signaling in macrophage migration and chemotaxis. J Leukocyte Biol 68, 593\u2013602 (2000).","journal-title":"J Leukocyte Biol"},{"key":"e_1_3_3_41_2","doi-asserted-by":"publisher","DOI":"10.1056\/NEJM199901143400207"}],"container-title":["Proceedings of the National Academy of Sciences"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/pnas.org\/doi\/pdf\/10.1073\/pnas.0908787106","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,5,27]],"date-time":"2023-05-27T17:37:31Z","timestamp":1685209051000},"score":1,"resource":{"primary":{"URL":"https:\/\/pnas.org\/doi\/full\/10.1073\/pnas.0908787106"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2009,12,29]]},"references-count":41,"journal-issue":{"issue":"52","published-print":{"date-parts":[[2009,12,29]]}},"alternative-id":["10.1073\/pnas.0908787106"],"URL":"https:\/\/doi.org\/10.1073\/pnas.0908787106","relation":{},"ISSN":["0027-8424","1091-6490"],"issn-type":[{"value":"0027-8424","type":"print"},{"value":"1091-6490","type":"electronic"}],"subject":[],"published":{"date-parts":[[2009,12,29]]},"assertion":[{"value":"2009-08-10","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2009-12-29","order":2,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}