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

Jie Shen, Shing Shun Tony To, Leslie Schrieber, Nicholas J.C. King

Research output: Journal article publicationJournal articleAcademic researchpeer-review

80 Citations (Scopus)


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-α) or interleukin 1 (IL-1) and could not be inhibited by neutralizing TNF-α, IL- α, or alpha/beta interferon (IFN-α/β) antibodies, suggesting a direct, virus-mediated phenomenon. TNF-α significantly enhanced WNV-induced increases in E-selectin, P-selectin, ICAM-1, and VCAM-1 expression, while IFN-γ 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-γ, TNF-α, or IL-1 acted in synergy with WNV to produce greater increases in MHC-I expression than WNV or cytokines alone, while IFN-α/β 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-α/β 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.
Original languageEnglish
Pages (from-to)9323-9332
Number of pages10
JournalJournal of Virology
Issue number12
Publication statusPublished - 1 Dec 1997

ASJC Scopus subject areas

  • Microbiology
  • Immunology
  • Insect Science
  • Virology

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