ECHOVIRUS-1 INFECTION INDUCES BOTH STRESS-ACTIVATED AND GROWTH-ACTIVATED MITOGEN-ACTIVATED PROTEIN-KINASE PATHWAYS AND REGULATES THE TRANSCRIPTION OF CELLULAR IMMEDIATE-EARLY GENES

We have previously shown that echovirus 1 (EV1) infection increases th e mRNA levels of cellular immediate-early (IE) genes in host cells. He re we provide further evidence that the induction of junB, c-jun, and c-fos genes is due to active Viral macromolecular synthesis rather tha n to the interaction of EV1 with its receptor, alpha(2)beta(1) integri n. Nuclear run-on transcription assays indicated that differences in m RNA levels in infected and uninfected cells are brought about by regul ation at the transcriptional level. EV1 infection induced the phosphor ylation of both the stress-related p38 mitogen-activated protein kinas e (MAPK) and the growth signal-related ERK1/2 MAPKs. Studies with sele ctive MAPK inhibitors revealed that p38 was the main inducer of junB e xpression, whereas both MAPK pathways were involved in the induction o f c-fos. Activation of AP-1 genes was also observed to occur during in fections with other enteroviruses and with Semliki Forest A7(74) virus , suggesting that the phosphorylation of MAPKs and induction of AP-1 g ene expression may be important regulators of host cell behavior durin g viral infections. (C) 1998 Academic Press.