title: Differences in Early Cytokine Production Are Associated With Development of a Greater Number of Symptoms Following West Nile Virus Infection.
abstract: West Nile virus (WNV) is an emerging cause of meningitis and encephalitis in the United States. Although severe neuroinvasive disease and death can occur in rare instances, the majority of infected individuals remain asymptomatic or present with a range of clinical manifestations associated with West Nile fever.
  
  
  
  To better understand the interindividual variability associated with the majority of WNV infections, we evaluated the association of cytokine/chemokine production and outcome of infection among 115 WNV-positive US blood donors identified in 2008-2011. All subjects self-reported symptoms as having occurred during the 2 weeks following blood donation, using a standardized questionnaire.
  
  
  
  We discovered that, prior to seroconversion, an early potent, largely type I interferon-mediated response correlated with development of a greater number of symptoms in WNV-infected individuals. Interestingly, individuals who developed fewer symptoms had not only a more modest type I interferon response initially, but also a protracted cytokine response after seroconversion, marked by the production of monocyte and T-cell-associated chemokines.
  
  
  
  Collectively, our data suggest that, although an early type I interferon response appears to be crucial to control WNV infection, successful immunity may require a modest early response that is maintained during the course of infection.
authors.affiliation: Department of Microbiology.
authors.forename: Kevin W
authors.initials: KW
authors.lastname: Hoffman
authors.affiliation: Department of Genetics and Genomics, Icahn School of Medicine at Mount Sinai, New York, New York.
authors.forename: David
authors.initials: D
authors.lastname: Sachs
authors.affiliation: Department of Microbiology.
authors.forename: Susana V
authors.initials: SV
authors.lastname: Bardina
authors.affiliation: Department of Microbiology.
authors.forename: Daniela
authors.initials: D
authors.lastname: Michlmayr
authors.affiliation: Department of Microbiology.
authors.forename: Carlos A
authors.initials: CA
authors.lastname: Rodriguez
authors.affiliation: Department of Microbiology.
authors.forename: Janet
authors.initials: J
authors.lastname: Sum
authors.affiliation: American Red Cross, Gaithersburg, Maryland.
authors.forename: Gregory A
authors.initials: GA
authors.lastname: Foster
authors.affiliation: American Red Cross, Gaithersburg, Maryland.
authors.forename: David
authors.initials: D
authors.lastname: Krysztof
authors.affiliation: American Red Cross, Gaithersburg, Maryland.
authors.forename: Susan L
authors.initials: SL
authors.lastname: Stramer
authors.affiliation: Department of Microbiology.
authors.forename: Jean K
authors.initials: JK
authors.lastname: Lim
mesh_terms: D000328:Adult; D000368:Aged; D001782:Blood Donors; D016207:Cytokines / Q000378:metabolism*; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D007370:Interferon Type I / Q000378:metabolism; D008297:Male; D008875:Middle Aged; D011795:Surveys and Questionnaires; D014481:United States; D014901:West Nile Fever / Q000276:immunology* / Q000473:pathology*; D014902:West Nile virus / Q000276:immunology*
chemical_list: D016207:Cytokines; D007370:Interferon Type I
keywords: blood bank; blood donations; clinical outcome; early symptomatology; susceptibility