Early induction of interferon-independent virus-specific ICAM-1 (CD54) expression by flavivirus in quiescent but not proliferating fibroblasts--implications for virus-host interactions.

West Nile Virus (WNV) infection of human embryonic fibroblasts can induce expression of ICAM-1 by two distinct mechanisms. An early and direct mechanism occurs within 2 hr of virus infection which is cytokine independent, and an indirect mechanism occurs within 24 hr of virus infection and is regulated by the release of IFN-type 1. Virus-inactivated, conditioned supernatants removed from WNV-infected fibroblast cultures at 4 hr did not alter ICAM-1 expression on fresh, untreated fibroblasts, whereas conditioned supernatants from 24-hr-infected cultures induced small increases in ICAM-1 expression after incubation for 24 hr but not after 4 hr. These studies also demonstrate that the expression of ICAM-1 on fibroblasts in response to flavivirus is cell-cycle dependent. WNV can only induce increased ICAM-1 expression in quiescent fibroblasts in G0 phase. In contrast, induction of ICAM-1 after exposure to types 1 and 2 IFN is not cell-cycle dependent. Other viruses, including double-stranded DNA viruses, vaccinia, and adenovirus 2 and 5 and the single, positive-stranded RNA alphavirus, Semiliki Forest virus, did not induce ICAM-1 expression on fibroblasts after 24 hr. Another alphavirus, Ross river, was able to induce ICAM-1 but only by the indirect mechanism of type 1 IFN-dependent release. The closely related flavivirus, Kunjin, induced increased ICAM-1 expression in a manner similar to WNV. The ability of flaviviruses to induce increased ICAM-1 expression directly within a few hours of infection may be an important virus-host survival strategy promoting cell-cell adhesion and hence possible further viral infection/replication.