ECHOVIRUS-1 REPLICATION, NOT ONLY VIRUS BINDING TO ITS RECEPTOR, VLA-2, IS REQUIRED FOR THE INDUCTION OF CELLULAR IMMEDIATE-EARLY GENES

Induction of immediate-early genes c-jun,junB, and c-fos was demonstra ted during echovirus 1 infection in a human osteogenic sarcoma (HOS) c ell line, Tenfold induction was seen at 10 h postinfection, correspond ing approximately to the end of the first replication cycle of the vir us. Echovirus 1 uses VLA-2 integrin as its cellular receptor, and liga nd binding by integrin is known to trigger signal transduction pathway s ultimately activating immediate-early genes, In the present study, h owever, VLA-2 binding alone was not sufficient to induce their express ion; viral replication was needed. This conclusion was based on the ob servations that no stimulation of the immediate-early genes occurred i n the MG-63 cell line where the virus attached only to VLA-2 but was n ot able to replicate and that induction of these genes was observed wh en the HOS cells were infected with echovirus type 7, known to use a d ifferent cellular receptor, Induction was not seen in the presence of the antiviral compound WIN 54954, which evidently inhibits the uncoati ng but not receptor binding of echovirus 1, suggesting that viral repl ication triggers the activation of the immediate-early genes, The indu ction of these genes may have a role in viral replication and in the p athogenesis of infection.