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 endot helial cells significantly increased 30 min postinfection with the fla vivirus West Nile virus (WNV), was maximal by 2 h postinfection, and d eclined to baseline levels within 24 h. Expression of ICAM-1 (CD54) an d 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 fact or alpha (TNF-alpha) or interleukin 1 (IL-1) and could not be inhibite d by neutralizing TNF-alpha, IL-1 alpha, or alpha/beta Interferon (IFN -alpha/beta) antibodies, suggesting a direct, virus-mediated phenomeno n. TNF-alpha significantly enhanced WNV-induced increases in E-selecti n, P-selectin, ICAM-1, and VCAM-1 expression, while IFN-gamma enhanced WNV-induced ICAM-1 expression. In contrast, IL-4 abrogated WNV-induce d E-selectin expression increases but acted in synergy with WNV to inc rease P-selectin and VCAM-1 expression. WNV increased the expression o f class I and II major histocompatibility complex antigens (MHC-I and MHC-II, respectively) at 24 and 72 h, respectively. IFN-gamma, TNF-alp ha, 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 sugg est sequential adhesion of leukocyte subpopulations to infected endoth elial cells, which may be important in initial viral spread in vivo.