title: In vitro evaluation of the protective role of human antibodies to West Nile virus (WNV) produced during natural WNV infection.
abstract: BACKGROUND
  West Nile virus (WNV) is endemic in the United States and transmissible by transfusion. Since 2003, the US blood supply has been screened by nucleic-acid tests (NAT) for WNV in minipools (MP-NAT) of 6 or 16 specimens. WNV infection begins with low-level viremia detectable only by individual testing (ID-NAT) and no detectable WNV antibodies. Viremia then increases to levels detectable by MP-NAT, and antibodies become detectable; later, viremia decays to levels detectable only by ID-NAT before becoming undetectable. All but 1 documented WNV transmission by transfusion involved blood components negative for WNV antibodies, raising the question whether WNV antibody-positive blood components with low levels of WNV RNA are infectious.
  
  
  METHODS
  Specimens from 102 viremic donors with and without WNV antibodies were used to investigate infectivity in cultures of Vero cells and human monocyte-derived macrophages (MDMs).
  
  
  RESULTS
  In Vero cell culture, 54 (74%) of 73 WNV antibody-negative specimens and 10 (36%) of 28 WNV antibody-positive specimens were infectious. In a random subset of 20 specimens tested in MDM culture, 7 (88%) of 8 WNV antibody-positive specimens and 12 (100%) of 12 WNV antibody-negative specimens were infectious.
  
  
  CONCLUSIONS
  WNV antibodies do not always protect susceptible cells from WNV infection in vitro. RNA positivity in the presence of antibody cannot be ignored as a theoretical risk for blood recipients and needs further investigation.
authors.affiliation: Laboratory of Molecular Virology-Division of Emerging Transfusion Transmitted Diseases, Office of Blood Research and Review, Center for Biologics Evaluation and Research, Food and Drug Administration, Bethesda, MD, USA. Maria.Rios@fda.hhs.gov
authors.forename: M
authors.initials: M
authors.lastname: Rios
authors.forename: S
authors.initials: S
authors.lastname: Daniel
authors.forename: A I
authors.initials: AI
authors.lastname: Dayton
authors.forename: O
authors.initials: O
authors.lastname: Wood
authors.forename: I K
authors.initials: IK
authors.lastname: Hewlett
authors.forename: J S
authors.initials: JS
authors.lastname: Epstein
authors.forename: S
authors.initials: S
authors.lastname: Caglioti
authors.forename: S L
authors.initials: SL
authors.lastname: Stramer
mesh_terms: D000818:Animals; D000914:Antibodies, Viral / Q000097:blood* / Q000276:immunology*; D002522:Chlorocebus aethiops; D006801:Humans; D008264:Macrophages / Q000821:virology; D012367:RNA, Viral / Q000097:blood; D014709:Vero Cells; D019562:Viral Load; D014766:Viremia; D014901:West Nile Fever / Q000276:immunology*; D014902:West Nile virus / Q000276:immunology*
chemical_list: D000914:Antibodies, Viral; D012367:RNA, Viral