INTERLEUKIN-8 SELECTIVELY ENHANCES CYTOPATHIC EFFECT (CPE) INDUCED BYPOSITIVE-STRAND RNA VIRUSES IN THE HUMAN WISH CELL-LINE

Interleukin-8 (IL-8), a proinflammatory chemokine, is induced by virus es and appears in circulation during viral infections, We found that I L-8 enhanced cytopathic effect induced by the positive strand RNA viru s, encephalomyocarditis virus (EMCV), in the human WISH cell line, The enhancement was dependent on IL-8 dose and virus dose and was reversi ble by specific monoclonal antibodies to IL-8. The chemokine was also able to increase EMC viral RNA synthesis and infectious virus yield. T his IL-8 enhancing action was not observed in the case of the negative strand RNA virus, vesicular stomatitis virus (VSV), ill WISH cells. W e examined the activity of constitutive 2',5'-oligoadenylate synthetas e (GAS), a pathway that was implicated in protection from EMCV but not VSV. The IL-8 action in EMCV-infected cells, unlike VSV-infected cell s, was associated with decreased OAS activity in a manner that was ind ependent of OAS gene expression, Understanding mechanisms of cytokine enhancement of viral activity may lead to novel ways to control viral infections. (C) 1997 Academic Press.