title: A new arenavirus in a cluster of fatal transplant-associated diseases.
abstract: BACKGROUND
  Three patients who received visceral-organ transplants from a single donor on the same day died of a febrile illness 4 to 6 weeks after transplantation. Culture, polymerase-chain-reaction (PCR) and serologic assays, and oligonucleotide microarray analysis for a wide range of infectious agents were not informative.
  
  
  METHODS
  We evaluated RNA obtained from the liver and kidney transplant recipients. Unbiased high-throughput sequencing was used to identify microbial sequences not found by means of other methods. The specificity of sequences for a new candidate pathogen was confirmed by means of culture and by means of PCR, immunohistochemical, and serologic analyses.
  
  
  RESULTS
  High-throughput sequencing yielded 103,632 sequences, of which 14 represented an Old World arenavirus. Additional sequence analysis showed that this new arenavirus was related to lymphocytic choriomeningitis viruses. Specific PCR assays based on a unique sequence confirmed the presence of the virus in the kidneys, liver, blood, and cerebrospinal fluid of the recipients. Immunohistochemical analysis revealed arenavirus antigen in the liver and kidney transplants in the recipients. IgM and IgG antiviral antibodies were detected in the serum of the donor. Seroconversion was evident in serum specimens obtained from one recipient at two time points.
  
  
  CONCLUSIONS
  Unbiased high-throughput sequencing is a powerful tool for the discovery of pathogens. The use of this method during an outbreak of disease facilitated the identification of a new arenavirus transmitted through solid-organ transplantation.
authors.affiliation: Center for Infection and Immunity, Mailman School of Public Health, Columbia University, New York, NY 10032, USA.
authors.forename: Gustavo
authors.initials: G
authors.lastname: Palacios
authors.forename: Julian
authors.initials: J
authors.lastname: Druce
authors.forename: Lei
authors.initials: L
authors.lastname: Du
authors.forename: Thomas
authors.initials: T
authors.lastname: Tran
authors.forename: Chris
authors.initials: C
authors.lastname: Birch
authors.forename: Thomas
authors.initials: T
authors.lastname: Briese
authors.forename: Sean
authors.initials: S
authors.lastname: Conlan
authors.forename: Phenix-Lan
authors.initials: PL
authors.lastname: Quan
authors.forename: Jeffrey
authors.initials: J
authors.lastname: Hui
authors.forename: John
authors.initials: J
authors.lastname: Marshall
authors.forename: Jan Fredrik
authors.initials: JF
authors.lastname: Simons
authors.forename: Michael
authors.initials: M
authors.lastname: Egholm
authors.forename: Christopher D
authors.initials: CD
authors.lastname: Paddock
authors.forename: Wun-Ju
authors.initials: WJ
authors.lastname: Shieh
authors.forename: Cynthia S
authors.initials: CS
authors.lastname: Goldsmith
authors.forename: Sherif R
authors.initials: SR
authors.lastname: Zaki
authors.forename: Mike
authors.initials: M
authors.lastname: Catton
authors.forename: W Ian
authors.initials: WI
authors.lastname: Lipkin
mesh_terms: D000328:Adult; D000914:Antibodies, Viral / Q000097:blood; D001117:Arenaviridae Infections / Q000635:transmission / Q000821:virology*; D018050:Arenavirus / Q000145:classification* / Q000235:genetics / Q000302:isolation & purification; D019295:Computational Biology; D018562:Disease Transmission, Infectious; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D007668:Kidney / Q000648:ultrastructure / Q000821:virology; D016030:Kidney Transplantation / Q000009:adverse effects*; D016031:Liver Transplantation / Q000009:adverse effects*; D008875:Middle Aged; D020411:Oligonucleotide Array Sequence Analysis; D016133:Polymerase Chain Reaction / Q000379:methods; D012367:RNA, Viral / Q000032:analysis; D017422:Sequence Analysis, DNA / Q000379:methods*
chemical_list: D000914:Antibodies, Viral; D012367:RNA, Viral