The α Chemokine, Interleukin 8, Inhibits the Antiviral Action of Interferon α

Abstract

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-α 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-α antiviral activity was associated with reduced 2′,5′-A oligoadenylate synthetase activity, a pathway well correlative with the anti– encephalomyocarditis virus action of IFN-α. Understanding pathways that antagonize IFN action may lead to novel approaches to potentiate endogenous and therapeutic IFN.

How Ebola and Marburg viruses battle the immune system

“…Moreover, the effects of VP35, VP24 and perhaps other filoviral proteins might prove even more pleiotropic -not only IFN-related genes but also multiple cellular genes were perturbed by filoviral infection of hepatocytes, many of these genes were differently dysregulated depending on the filovirus species 28 . Further, it was shown previously that interleukin-8 (IL-8; also known as CXC-chemokine ligand 8 (CXCL8)), an α-chemokine produced abundantly during filoviral infection, antagonizes the antiviral activity of IFNα by inhibiting the function of 2′,5′-oligoadenylate synthetase (OAS) in encephalomyocarditis virus (EMCV) infection 29 . Accordingly, it may be worthwhile to explore the role of IL-8 in filoviral infections.…”

Potential involvement of IL-8 in the pathogenesis of human cytomegalovirus infection

“…Encephalomyocarditis virus (EMCV) was propagated in L929 cells [15]. Recombinant human IL-8 was generously provided by Dainippon Pharmaceuticals (Osaka, Japan).…”

“…Hence, we explored the effects of CMV infection on IL-8 production by a monocytic cell line, THP-1 [13]. In addition, in order to elucidate the interaction between host response and CMV infection, we also examined the effects of IL-8 on CMV replication [14] and antiviral actions of interferon (IFN)-␣ [15].…”

Regulation of CXCL-8 (Interleukin-8) Induction by Double-Stranded RNA Signaling Pathways during Hepatitis C Virus Infection

“…For example, CXCL-8 is induced in response to the expression of the HCV NS5A protein (3, 4, 16, 50) and HCV replication (19). Moreover, CXCL-8 inhibits the antiviral actions of IFN-␣ (29), and recent studies indicate that CXCL-8 protein levels are associated with HCV replication (30).…”