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.
Shen
J
J
Department of Pathology, University of Sydney, N.S.W., Australia.
Devery
J M
JM
King
N J
NJ
D000260:Adenoviruses, Human / Q000502:physiology; D002450:Cell Communication; D002478:Cells, Cultured; D018349:Encephalitis Viruses, Japanese / Q000502:physiology*; D005347:Fibroblasts; D006801:Humans; D018799:Intercellular Adhesion Molecule-1 / Q000096:biosynthesis*; D016899:Interferon-beta / Q000494:pharmacology; D007371:Interferon-gamma / Q000494:pharmacology; D007399:Interphase; D007700:Kinetics; D011070:Poly I-C / Q000494:pharmacology; D012398:Ross River virus / Q000502:physiology; D012672:Semliki forest virus / Q000502:physiology; D014616:Vaccinia virus / Q000502:physiology; D014902:West Nile virus / Q000502:physiology*
D018799:Intercellular Adhesion Molecule-1; D016899:Interferon-beta; D007371:Interferon-gamma; D011070:Poly I-C