Early E-selectin, VCAM-1, ICAM-1, and late major histocompatibility complex antigen induction on human endothelial cells by flavivirus and comodulation of adhesion molecule expression by immune cytokines.
Expression of E-selectin (ELAM-1, CD62E) on human umbilical vein endothelial cells significantly increased 30 min postinfection with the flavivirus West Nile virus (WNV), was maximal by 2 h postinfection, and declined to baseline levels within 24 h. Expression of ICAM-1 (CD54) and VCAM-1 (CD106) was significantly increased by 2 h and maximal at 4 h after infection. P-selectin (CD62P) expression was unaffected by WNV. Upregulation occurred earlier than that caused by tumor necrosis factor alpha (TNF-alpha) or interleukin 1 (IL-1) and could not be inhibited by neutralizing TNF-alpha, IL-1alpha, or alpha/beta interferon (IFN-alpha/beta) antibodies, suggesting a direct, virus-mediated phenomenon. TNF-alpha significantly enhanced WNV-induced increases in E-selectin, P-selectin, ICAM-1, and VCAM-1 expression, while IFN-gamma enhanced WNV-induced ICAM-1 expression. In contrast, IL-4 abrogated WNV-induced E-selectin expression increases but acted in synergy with WNV to increase P-selectin and VCAM-1 expression. WNV increased the expression of class I and II major histocompatibility complex antigens (MHC-I and MHC-II, respectively) at 24 and 72 h, respectively. IFN-gamma, TNF-alpha, or IL-1 acted in synergy with WNV to produce greater increases in MHC-I expression than WNV or cytokines alone, while IFN-alpha/beta or IL-4 had no effect. MHC-II induction in cytokine-treated, WNV-infected cells was similar to that caused by cytokines alone. Neutralizing IFN-alpha/beta antibody inhibited WNV-induced MHC-I expression by 30% at 24 h and by 100% by 72 h. The differential kinetics of modulation suggest sequential adhesion of leukocyte subpopulations to infected endothelial cells, which may be important in initial viral spread in vivo.
Shen
J
J
Department of Pathology, University of Sydney, New South Wales, Australia.
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Schrieber
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King
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D000818:Animals; D000911:Antibodies, Monoclonal / Q000276:immunology; D015703:Antigens, CD / Q000096:biosynthesis*; D015815:Cell Adhesion Molecules / Q000096:biosynthesis*; D002478:Cells, Cultured; D002522:Chlorocebus aethiops; D016207:Cytokines / Q000276:immunology*; D019040:E-Selectin / Q000096:biosynthesis; D004730:Endothelium, Vascular / Q000166:cytology / Q000276:immunology*; D005416:Flavivirus / Q000276:immunology; D006680:HLA Antigens / Q000096:biosynthesis*; D006801:Humans; D018799:Intercellular Adhesion Molecule-1 / Q000096:biosynthesis; D019007:P-Selectin / Q000096:biosynthesis; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology; D014471:Umbilical Veins / Q000166:cytology / Q000276:immunology; D019010:Vascular Cell Adhesion Molecule-1 / Q000096:biosynthesis; D014709:Vero Cells; D014902:West Nile virus / Q000276:immunology*
D000911:Antibodies, Monoclonal; D015703:Antigens, CD; D015815:Cell Adhesion Molecules; D016207:Cytokines; D019040:E-Selectin; D006680:HLA Antigens; D019007:P-Selectin; D014409:Tumor Necrosis Factor-alpha; D019010:Vascular Cell Adhesion Molecule-1; D018799:Intercellular Adhesion Molecule-1