Interferon regulatory factor-3 activation in adenovirus infection

Abstract

Adenovirus (Ad) infection is accompanied by an early inflammatory response that is stimulated by the binding and/or entry of the Ad capsid to the cell. Several studies have linked NF-kappaB to the activation of pro-inflammatory cytokines and chemokines early in Ad infection, however, for many other viruses, another key transcription factor, Interferon Regulatory Factor 3 (IRF-3), also acts early in viral infection. We sought to determine if IRF-3 is activated upon Ad infection, and to examine its importance in establishing an anti-viral state in Ad-infected cells. Our data suggests that wtAd5 infection results in phosphorylation of IRF-3 on a novel amino acid residue, and this event is dependent on virus replication. Moreover, IRF-3 is an important transcription factor for induction of RANTES expression in wtAd5-infected cells. Taken together, these data suggest that IRF-3 activation in response to Ad DNA replication is important in establishing an anti-viral state within the infected cell.