Cell-adhesion and spread are important for cell survival. Although extensive studies have suggested several potential mechanisms of action, it is not yet clear how important cell-morphological change per se contributes to the cell-surviving signal. We employed a non-integrin-mediated cell-adhesion system to explore this question. BHK—Japanese encephalitis virus (JEV) cells (BHK21 cells that are persistently infected with JEV) express a large amount of JEV-envelope protein (JEV E) on their surfaces, and can attach and form pseudopodia on the anti-JEV E antibody-coated substrates. However, cells that adhered on the antibody substrate underwent a caspase-3-mediated apoptosis together with a down-regulation of mitogen-activated protein kinase activity within 20 h after adhesion, which indicates that viral-protein-mediated cell-adhesion and cell-spread are not sufficient for supporting cell survival. This provides a different perspective for the study of the relationships between the cell-morphological change and the cell-survival signal.