Publication Date
9-4-2023
Journal
Journal of Experimental Medicine
DOI
10.1084/jem.20230661
PMID
37347462
PMCID
PMC10287549
PubMedCentral® Posted Date
6-22-2023
PubMedCentral® Full Text Version
Post-print
Published Open-Access
yes
Keywords
Animals, Chlorocebus aethiops, Humans, West Nile Fever, West Nile virus, Vero Cells, Autoantibodies, Antibodies, Viral, Interferon Type I, Interferon-alpha
Abstract
Mosquito-borne West Nile virus (WNV) infection is benign in most individuals but can cause encephalitis in <1% of infected individuals. We show that ∼35% of patients hospitalized for WNV disease (WNVD) in six independent cohorts from the EU and USA carry auto-Abs neutralizing IFN-α and/or -ω. The prevalence of these antibodies is highest in patients with encephalitis (∼40%), and that in individuals with silent WNV infection is as low as that in the general population. The odds ratios for WNVD in individuals with these auto-Abs relative to those without them in the general population range from 19.0 (95% CI 15.0–24.0, P value <10–15) for auto-Abs neutralizing only 100 pg/ml IFN-α and/or IFN-ω to 127.4 (CI 87.1–186.4, P value <10–15) for auto-Abs neutralizing both IFN-α and IFN-ω at a concentration of 10 ng/ml. These antibodies block the protective effect of IFN-α in Vero cells infected with WNV in vitro. Auto-Abs neutralizing IFN-α and/or IFN-ω underlie ∼40% of cases of WNV encephalitis.