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

Abstract

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-␣) or interleukin 1 (IL-1) and could not be inhibited by neutralizing TNF-␣, IL-1␣, or alpha/beta interferon (IFN-␣/␤) antibodies, suggesting a direct, virus-mediated phenomenon. TNF-␣ significantly enhanced WNV-induced increases in E-selectin, P-selectin, ICAM-1, and VCAM-1 expression, while IFN-␥ 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-␥, TNF-␣, or IL-1 acted in synergy with WNV to produce greater increases in MHC-I expression than WNV or cytokines alone, while IFN-␣/␤ 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-␣/␤ 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.

Dengue virus infection of human microvascular endothelial cells from different vascular beds promotes both common and specific functional changes

“…Microvascular endothelial cells are an active interface between blood immune cells and tissues. Many stimuli of which vasoactive compounds but also several pathogens [Shen et al, 1997;Knight et al, 1999;Sundstrom et al, 2001;Caruso et al, 2002;De Maula et al, 2002;Hippenstiel and Suttorp, 2003] induce endothelial cells to change from a physiological state to a pro-inflammatory and pro-adhesive state. This is most often characterized by increased production of inflammatory soluble mediators and by over-expression of cell surface molecules, that is adhesion molecules, HLA antigens, and others, involved in the cross talk between endothelial cells and circulating immune cells.…”

Variations in Biological Features of West Nile Viruses

“…Human umbilical vein endothelial cells (HUVEC) can be infected with WN virus. 57 WN virus infection increased the expression of E-selectin, VCAM-I, and ICAM-I within 30 min to 3 h after infection. Infected endothelial cells also produce nitric oxide that may potentiate monocyte adhesion.…”

Immunopathology of flavivirus infections

“…Flavivirus infection of endothelium in vitro also leads to upregulated adhesion as well as MHC molecules, which in turn can be modulated by cytokines. 55 In vivo, this increased ICAM-1 expression is detectable several days before WNV is detected in the brain. 49 The activation of Toll-like receptors 3 (TLR3), by WNV, indirectly enhances the permeability of the BBB via tumour necrosis factor (TNF).…”