title: Association between high expression macrophage migration inhibitory factor (MIF) alleles and West Nile virus encephalitis.
abstract: Infection with mosquito-borne West Nile virus (WNV) is usually asymptomatic but can lead to severe WNV encephalitis. The innate cytokine, macrophage migration inhibitory factor (MIF), is elevated in patients with WNV encephalitis and promotes viral neuroinvasion and mortality in animal models. In a case-control study, we examined functional polymorphisms in the MIF locus in a cohort of 454 North American patients with neuroinvasive WNV disease and found patients homozygous for high-expression MIF alleles to be >20-fold (p=0.008) more likely to have WNV encephalitis. These data indicate that MIF is an important determinant of severity of WNV neuropathogenesis and may be a therapeutic target.
authors.affiliation: Department of Internal Medicine, Yale School of Medicine, New Haven, CT, United States; University of Pennsylvania School of Medicine, Philadelphia, PA, United States.
authors.forename: Rituparna
authors.initials: R
authors.lastname: Das
authors.affiliation: Department of Internal Medicine, Yale School of Medicine, New Haven, CT, United States.
authors.forename: Kerry
authors.initials: K
authors.lastname: Loughran
authors.affiliation: Department of Internal Medicine, Yale School of Medicine, New Haven, CT, United States.
authors.forename: Charles
authors.initials: C
authors.lastname: Murchison
authors.affiliation: Department of Internal Medicine, Yale School of Medicine, New Haven, CT, United States.
authors.forename: Feng
authors.initials: F
authors.lastname: Qian
authors.affiliation: Department of Internal Medicine, Yale School of Medicine, New Haven, CT, United States.
authors.forename: Lin
authors.initials: L
authors.lastname: Leng
authors.affiliation: Department of Internal Medicine, Yale School of Medicine, New Haven, CT, United States.
authors.forename: Yan
authors.initials: Y
authors.lastname: Song
authors.affiliation: Department of Internal Medicine, Yale School of Medicine, New Haven, CT, United States. Electronic address: ruth.montgomery@yale.edu.
authors.forename: Ruth R
authors.initials: RR
authors.lastname: Montgomery
authors.affiliation: McMaster University, Ontario, Canada.
authors.forename: Mark
authors.initials: M
authors.lastname: Loeb
authors.affiliation: Department of Internal Medicine, Yale School of Medicine, New Haven, CT, United States.
authors.forename: Richard
authors.initials: R
authors.lastname: Bucala
mesh_terms: D000328:Adult; D000368:Aged; D000483:Alleles; D016022:Case-Control Studies; D005260:Female; D015870:Gene Expression; D056726:Genetic Association Studies; D020022:Genetic Predisposition to Disease; D005838:Genotype; D006801:Humans; D019746:Intramolecular Oxidoreductases / Q000235:genetics*; D008263:Macrophage Migration-Inhibitory Factors / Q000235:genetics*; D008297:Male; D008875:Middle Aged; D014901:West Nile Fever / Q000150:complications / Q000235:genetics / Q000276:immunology* / Q000821:virology; D014902:West Nile virus / Q000276:immunology / Q000472:pathogenicity; D055815:Young Adult
chemical_list: D008263:Macrophage Migration-Inhibitory Factors; D019746:Intramolecular Oxidoreductases; C515598:MIF protein, human
keywords: Immune response; Macrophage; Mosquito vector; Neurologic disease; West Nile virus