The alpha chemokine, interleukin 8, inhibits the antiviral action of interferon alpha.
Interferon (IFN) exhibits a potent antiviral activity in vitro and plays a major role in the early defense against viruses. Like IFN, the proinflammatory chemokine, interleukin (IL)-8, is induced by viruses and appears in circulation during viral infections. In an in vitro cytopathic effect assay for IFN, we found that IL-8 can inhibit IFN-alpha activity in a dose-dependent manner. This action was reversed by specific monoclonal antibodies to IL-8. The chemokine was able to attenuate the IFN-mediated inhibition of viral replication as determined by measuring infectious virus yield. IL-8 also diminished the ability of IFN to inhibit an early stage of viral replication since IL-8 attenuated the inhibition of the formation of viral proteins. It appeared that IL-8 interfered with a late rather than an early step of IFN-mediated pathway such as early gene expression. The IL-8 inhibitory action on IFN-alpha antiviral activity was associated with reduced 2',5'-A oligoadenylate synthetase activity, a pathway well correlative with the anti- encephalomyocarditis virus action of IFN-alpha. Understanding pathways that antagonize IFN action may lead to novel approaches to potentiate endogenous and therapeutic IFN.
Khabar
K S
KS
Department of Biological and Medical Research, King Faisal Specialist Hospital & Research Center, Riyadh, Saudi Arabia 11211, USA. khabar@kfshrc.edu.sa
Al-Zoghaibi
F
F
Al-Ahdal
M N
MN
Murayama
T
T
Dhalla
M
M
Mukaida
N
N
Taha
M
M
Al-Sedairy
S T
ST
Siddiqui
Y
Y
Kessie
G
G
Matsushima
K
K
D015088:2',5'-Oligoadenylate Synthetase / Q000378:metabolism; D000818:Animals; D000911:Antibodies, Monoclonal / Q000276:immunology; D015703:Antigens, CD / Q000235:genetics; D000998:Antiviral Agents / Q000037:antagonists & inhibitors*; D001667:Binding, Competitive; D002460:Cell Line; D002470:Cell Survival; D002522:Chlorocebus aethiops; D003588:Cytopathogenic Effect, Viral; D004305:Dose-Response Relationship, Drug; D015967:Gene Expression Regulation, Viral; D006801:Humans; D016898:Interferon-alpha / Q000037:antagonists & inhibitors*; D016209:Interleukin-8 / Q000276:immunology / Q000494:pharmacology*; D010849:Picornaviridae / Q000502:physiology; D012333:RNA, Messenger / Q000378:metabolism; D018123:Receptors, Interleukin / Q000235:genetics; D023062:Receptors, Interleukin-8A; D011994:Recombinant Proteins / Q000494:pharmacology; D014709:Vero Cells; D014721:Vesicular stomatitis Indiana virus / Q000502:physiology; D014764:Viral Proteins / Q000096:biosynthesis; D014779:Virus Replication
D000911:Antibodies, Monoclonal; D015703:Antigens, CD; D000998:Antiviral Agents; D016898:Interferon-alpha; D016209:Interleukin-8; D012333:RNA, Messenger; D018123:Receptors, Interleukin; D023062:Receptors, Interleukin-8A; D011994:Recombinant Proteins; D014764:Viral Proteins; D015088:2',5'-Oligoadenylate Synthetase