POTENTIAL INVOLVEMENT OF IL-8 IN THE PATHOGENESIS OF HUMAN CYTOMEGALOVIRUS-INFECTION

The observations that several types of viruses induced interleukin (IL )-8 production prompted us to investigate the interrelationship betwee n IL-8 and cytomegalovirus (CMV) infection. CMV infection caused IL-8 production in a human monocytic cell line, THP-1, in dose-and time-dep endent manners. Moreover, CMV induced IL-8 gene expression by concurre ntly activating transcription factors, NF-kappa B and AP-1, Furthermor e, CMV infection of human fibroblast cell lines increased gene express ion of a specific receptor for IL-8, CXCR1. IL-8 in turn enhanced CMV replication in a human embryonic fibroblast, MRC-5, in dose-and time-d ependent manners. Augmented replication eventually culminated in the i ncreased production of infectious CMV virions. Moreover, IL-8 can atte nuate the antiviral activity of interferon (IFN), particularly that of alpha-type against picornaviruses such as encephalomyocarditis virus and poliovirus. The inhibitory effects were associated with reduced 2' ,5'-A oligoadenylate synthetase activity. These results would imply th at CMV can induce IL-8, which can augment CMV replication directly and indirectly by counteracting antiviral activity of IFN.