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Updated: May 5, 2026
In Vitro Analysis of Myd88-mediated Cellular Immune Response to West Nile Virus Mutant Strain Infection
Published on: November 27, 2014
Abrogation of macrophage migration inhibitory factor decreases West Nile virus lethality by limiting viral
Alvaro Arjona1, Harald G Foellmer, Terrence Town
1Section of Rheumatology, Department of Internal Medicine, Yale University School of Medicine, New Haven, Connecticut, USA.
Abstract:
The flavivirus West Nile virus (WNV) is an emerging pathogen that causes life-threatening encephalitis in susceptible individuals. We investigated the role of the proinflammatory cytokine macrophage migration inhibitory factor (MIF), which is an upstream mediator of innate immunity, in WNV immunopathogenesis. We found that patients suffering from acute WNV infection presented with increased MIF levels in plasma and in cerebrospinal fluid. MIF expression also was induced in WNV-infected mice. Remarkably, abrogation of MIF action by 3 distinct approaches (antibody blockade, small molecule pharmacologic inhibition, and genetic deletion) rendered mice more resistant to WNV lethality. Mif(-/-) mice showed a reduced viral load and inflammatory response in the brain when compared with wild-type mice. Our results also indicate that MIF favors viral neuroinvasion by compromising the integrity of the blood-brain barrier. In conclusion, the data obtained from this study provide direct evidence for the involvement of MIF in viral pathogenesis and suggest that pharmacotherapeutic approaches targeting MIF may hold promise for the treatment of WNV encephalitis.
Insights
Macrophage migration inhibitory factor (MIF) exacerbates West Nile virus (WNV) encephalitis by increasing viral load and compromising the blood-brain barrier. Inhibiting MIF enhances resistance to WNV lethality, suggesting MIF as a therapeutic target.
Area of Science:
- Immunology
- Virology
- Neuroscience
Background:
- West Nile virus (WNV) causes severe encephalitis.
- Macrophage migration inhibitory factor (MIF) is a key innate immunity mediator.
Purpose of the Study:
- To investigate the role of MIF in WNV pathogenesis and encephalitis.
- To evaluate the therapeutic potential of targeting MIF in WNV infection.
Main Methods:
- Measured MIF levels in WNV-infected patients and mice.
- Used antibody blockade, small molecule inhibition, and genetic deletion to abrogate MIF function in mice.
- Assessed WNV lethality, viral load, brain inflammation, and blood-brain barrier integrity.
Main Results:
- Elevated MIF levels observed in plasma and cerebrospinal fluid of WNV-infected patients.
- MIF expression increased in WNV-infected mice.
- MIF inhibition significantly increased mouse survival and reduced viral load and neuroinflammation.
- MIF was found to compromise blood-brain barrier integrity, facilitating neuroinvasion.
Conclusions:
- MIF plays a critical role in WNV pathogenesis and encephalitis.
- Targeting MIF represents a promising therapeutic strategy for treating WNV encephalitis.
