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 between IL-8 and cytomegalovirus (CMV) infection. CMV infection caused IL-8 production in a human monocytic cell line, THP-1, in dose- and time-dependent manners. Moreover, CMV induced IL-8 gene expression by concurrently activating transcription factors, NF-kappaB and AP-1. Furthermore, CMV infection of human fibroblast cell lines increased gene expression 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-dependent manners. Augmented replication eventually culminated in the increased production of infectious CMV virions. Moreover, IL-8 can attenuate 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 that CMV can induce IL-8, which can augment CMV replication directly and indirectly by counteracting antiviral activity of IFN.
Murayama
T
T
Department of Microbiology, Kanazawa Medical University, Uchinada, Ishikawa, Japan.
Mukaida
N
N
Khabar
K S
KS
Matsushima
K
K
D000998:Antiviral Agents / Q000494:pharmacology; D002460:Cell Line; D003587:Cytomegalovirus / Q000502:physiology; D003586:Cytomegalovirus Infections / Q000188:drug therapy / Q000209:etiology* / Q000378:metabolism; D006801:Humans; D016898:Interferon-alpha / Q000494:pharmacology; D016209:Interleukin-8 / Q000096:biosynthesis / Q000494:pharmacology / Q000502:physiology*; D009000:Monocytes / Q000187:drug effects / Q000378:metabolism / Q000821:virology; D014779:Virus Replication / Q000187:drug effects
D000998:Antiviral Agents; D016898:Interferon-alpha; D016209:Interleukin-8