title: Viral binding-induced signaling drives a unique and extended intracellular trafficking pattern during infection of primary monocytes.
abstract: We initiated experiments to examine the infection of monocytes postentry. New data show that human cytomegalovirus (HCMV) DNA is detected in the nucleus beginning only at 3 d postinfection in monocytes, compared with 30 min postinfection in fibroblasts and endothelial cells, suggesting that HCMV nuclear translocation in monocytes is distinct from that seen in other cell types. We now show that HCMV is initially retained in early endosomes and then moves sequentially to the trans-Golgi network (TGN) and recycling endosomes before nuclear translocation. HCMV is retained initially as a mature particle before deenvelopment in recycling endosomes. Disruption of the TGN significantly reduced nuclear translocation of viral DNA, and HCMV nuclear translocation in infected monocytes was observed only when correct gH/gL/UL128-131/integrin/c-Src signaling occurred. Taken together, our findings show that viral binding of the gH/gL/UL128-131 complex to integrins and the ensuing c-Src signaling drive a unique nuclear translocation pattern that promotes productive infection and avoids viral degradation, suggesting that it represents an additional viral evasion/survival strategy.
authors.affiliation: Department of Microbiology and Immunology, Center for Molecular and Tumor Virology, Louisiana State University Health Sciences Center, Shreveport, LA 71130; Center for Cardiovascular Diseases and Sciences, Louisiana State University Health Sciences Center, Shreveport, LA 71130;
authors.forename: Jung Heon
authors.initials: JH
authors.lastname: Kim
authors.affiliation: Department of Microbiology and Immunology, Center for Molecular and Tumor Virology, Louisiana State University Health Sciences Center, Shreveport, LA 71130; Center for Cardiovascular Diseases and Sciences, Louisiana State University Health Sciences Center, Shreveport, LA 71130;
authors.forename: Donna
authors.initials: D
authors.lastname: Collins-McMillen
authors.affiliation: Vaccine and Gene Therapy Institute, Oregon Health & Science University, Beaverton, OR 97006;
authors.forename: Patrizia
authors.initials: P
authors.lastname: Caposio
authors.affiliation: Department of Microbiology and Immunology, Center for Molecular and Tumor Virology, Louisiana State University Health Sciences Center, Shreveport, LA 71130; Center for Cardiovascular Diseases and Sciences, Louisiana State University Health Sciences Center, Shreveport, LA 71130; Center of Excellence in Arthritis and Rheumatology, Louisiana State University Health Sciences Center, Shreveport, LA 71130; Feist-Weiller Cancer Center, Louisiana State University Health Sciences Center, Shreveport, LA 71130 ayuroc@lsuhsc.edu.
authors.forename: Andrew D
authors.identifier: 0000-0002-6452-5813
authors.initials: AD
authors.lastname: Yurochko
mesh_terms: D000081247:CSK Tyrosine-Protein Kinase; D002478:Cells, Cultured; D003587:Cytomegalovirus / Q000378:metabolism* / Q000502:physiology; D011992:Endosomes / Q000378:metabolism / Q000821:virology; D042783:Endothelial Cells / Q000378:metabolism / Q000821:virology; D005347:Fibroblasts / Q000378:metabolism / Q000821:virology; D054884:Host-Pathogen Interactions; D006801:Humans; D016023:Integrins / Q000378:metabolism; D008562:Membrane Glycoproteins / Q000378:metabolism; D009000:Monocytes / Q000378:metabolism* / Q000821:virology; D011485:Protein Binding; D021381:Protein Transport; D015398:Signal Transduction; D014759:Viral Envelope Proteins / Q000378:metabolism; D053585:Virus Attachment; D053586:Virus Internalization; D019061:src-Family Kinases / Q000378:metabolism; D021601:trans-Golgi Network / Q000378:metabolism / Q000821:virology
chemical_list: D016023:Integrins; D008562:Membrane Glycoproteins; C532797:UL128 protein, human cytomegalovirus; D014759:Viral Envelope Proteins; C071440:glycoprotein H, Cytomegalovirus; D000081247:CSK Tyrosine-Protein Kinase; D019061:src-Family Kinases; C000631346:CSK protein, human
keywords: gH/gL/UL128-131 complex; integrins; monocytes; nuclear translocation pathway; viral trafficking