Vaccinia virus induces Ca2+-independent cell-matrix adhesion during the motile phase of infection.
Vaccinia virus (VV) induces two forms of cell motility: cell migration, which is dependent on the expression of early genes, and the formation of cellular projections, which requires the expression of late genes. The need for viral gene expression prior to cell motility suggests that VV proteins may affect how infected cells interact with the extracellular matrix. To address this, we have analyzed changes in cell-matrix adhesion after infection of BS-C-1 cells with VV. Whereas uninfected cells round up and detach from the culture flask in the presence of EGTA, infected cells remain attached to the culture flask with a stellate morphology. Ca2+-independent cell-matrix adhesion was evident by 10 h postinfection, after the onset of cell motility but before the formation of virus-induced cellular projections. Progression to Ca2+-independent adhesion required the expression of late viral genes but not the formation of intracellular enveloped virus particles or intracellular actin tails. Analyses of specific matrix proteins identified vitronectin and fibronectin as optimal ligands for Ca2+-independent adhesion and the formation of cellular projections. Adhesion to fibronectin was mediated via RGD motifs alone and was not inhibited by 500 micrograms of heparin/ml. Kistrin, a disintegrin which binds preferentially to the alphav beta3 (vitronectin/fibronectin) receptor inhibited the formation of cellular projections without disrupting preformed matrix interactions. Finally, we show that Ca2+-independent cell-matrix adhesion is a dynamic process which mediates changes in the morphology of VV-infected cells and uninfected cells which exhibit a transformed phenotype.
Sanderson
C M
CM
Sir William Dunn School of Pathology, University of Oxford, Oxford OX1 3RE, United Kingdom.
Smith
G L
GL
D000818:Animals; D002118:Calcium / Q000378:metabolism; D002448:Cell Adhesion / Q000235:genetics / Q000502:physiology*; D002460:Cell Line; D002465:Cell Movement / Q000235:genetics / Q000502:physiology; D002472:Cell Transformation, Viral; D005109:Extracellular Matrix / Q000378:metabolism; D005353:Fibronectins / Q000737:chemistry / Q000378:metabolism; D015870:Gene Expression; D005814:Genes, Viral; D000882:Haplorhini; D009842:Oligopeptides; D010641:Phenotype; D014615:Vaccinia / Q000209:etiology / Q000378:metabolism / Q000473:pathology; D014616:Vaccinia virus / Q000235:genetics / Q000472:pathogenicity*
D005353:Fibronectins; D009842:Oligopeptides; C047981:arginyl-glycyl-aspartic acid; D002118:Calcium