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Interleukin-8 selectively enhances cytopathic effect (CPE) induced by positive-strand RNA viruses in the human WISH
K S Khabar1, F Al-Zoghaibi, T Murayama
1Department of Biological and Medical Research, King Faisal Specialist Hospital and Research Center, Riyadh, Saudi Arabia.
Abstract:
Interleukin-8 (IL-8), a proinflammatory chemokine, is induced by viruses and appears in circulation during viral infections. We found that IL-8 enhanced cytopathic effect induced by the positive strand RNA virus, encephalomyocarditis virus (EMCV), in the human WISH cell line. The enhancement was dependent on IL-8 dose and virus dose and was reversible by specific monoclonal antibodies to IL-8. The chemokine was also able to increase EMC viral RNA synthesis and infectious virus yield. This IL-8 enhancing action was not observed in the case of the negative strand RNA virus, vesicular stomatitis virus (VSV), in WISH cells. We examined the activity of constitutive 2',5'-oligoadenylate synthetase (OAS), a pathway that was implicated in protection from EMCV but not VSV. The IL-8 action in EMCV-infected cells, unlike VSV-infected cells, was associated with decreased OAS activity in a manner that was independent of OAS gene expression. Understanding mechanisms of cytokine enhancement of viral activity may lead to novel ways to control viral infections.
Insights
Interleukin-8 (IL-8) enhances viral infections by increasing viral RNA synthesis and replication. This inflammatory chemokine
Area of Science:
- Virology
- Immunology
- Molecular Biology
Background:
- Interleukin-8 (IL-8) is a proinflammatory chemokine present during viral infections.
- Viral infections can induce IL-8 production and circulation.
- The role of IL-8 in modulating viral activity requires further investigation.
Purpose of the Study:
- To investigate the effect of IL-8 on viral cytopathic effects and replication.
- To determine if IL-8's influence varies between different types of RNA viruses.
- To explore the underlying molecular mechanisms of IL-8's interaction with viral infections.
Main Methods:
- Utilized the human WISH cell line for viral infection models.
- Administered encephalomyocarditis virus (EMCV, positive-strand RNA) and vesicular stomatitis virus (VSV, negative-strand RNA).
- Assessed viral cytopathic effect, viral RNA synthesis, infectious virus yield, and 2',5'-oligoadenylate synthetase (OAS) activity.
Main Results:
- IL-8 significantly enhanced EMCV-induced cytopathic effect, viral RNA synthesis, and infectious virus yield in a dose-dependent manner.
- This enhancement was specific to the positive-strand RNA virus EMCV and not observed with the negative-strand RNA virus VSV.
- IL-8 treatment in EMCV-infected cells led to decreased constitutive 2',5'-oligoadenylate synthetase (OAS) activity, independent of OAS gene expression.
Conclusions:
- IL-8 acts as a potent enhancer of positive-strand RNA virus replication and pathogenesis.
- The observed effects of IL-8 are virus-specific and linked to modulation of cellular antiviral pathways like OAS.
- Understanding cytokine-mediated enhancement of viral activity may offer new therapeutic strategies for viral infections.