A new arenavirus in a cluster of fatal transplant-associated diseases

Gustavo F. Palacios; Julian Druce; Lei Du; Thomas Tran; Chris Birch; Thomas Briese; Sean Conlan; Phuong-Lan Quan; Jeffrey Hui; John Marshall; Jan Fredrik Simons; Michael Egholm; Christopher D. Paddock; Wun-Ju Shieh; Cynthia S. Goldsmith; Sherif R. Zaki; Mike Catton; W. Ian Lipkin

A new arenavirus in a cluster of fatal transplant-associated diseases
Palacios, Gustavo F.
Druce, Julian
Du, Lei
Tran, Thomas
Birch, Chris
Briese, Thomas
Conlan, Sean
Quan, Phuong-Lan
Hui, Jeffrey
Marshall, John
Simons, Jan Fredrik
Egholm, Michael
Paddock, Christopher D.
Shieh, Wun-Ju
Goldsmith, Cynthia S.
Zaki, Sherif R.
Catton, Mike
Lipkin, W. Ian
Center for Infection and Immunity
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New England Journal of Medicine
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. 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. 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.
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Gustavo F. Palacios, Julian Druce, Lei Du, Thomas Tran, Chris Birch, Thomas Briese, Sean Conlan, Phuong-Lan Quan, Jeffrey Hui, John Marshall, Jan Fredrik Simons, Michael Egholm, Christopher D. Paddock, Wun-Ju Shieh, Cynthia S. Goldsmith, Sherif R. Zaki, Mike Catton, W. Ian Lipkin, , A new arenavirus in a cluster of fatal transplant-associated diseases, Columbia University Academic Commons, .

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