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      Myeloablation-associated deletion of ORF4 in a human coronavirus 229E infection

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          Abstract

          We describe metagenomic next-generation sequencing (mNGS) of a human coronavirus 229E from a patient with AML and persistent upper respiratory symptoms, who underwent hematopoietic cell transplantation (HCT). mNGS revealed a 548-nucleotide deletion, which comprised the near entirety of the ORF4 gene, and no minor allele variants were detected to suggest a mixed infection. As part of her pre-HCT conditioning regimen, the patient received myeloablative treatment with cyclophosphamide and 12 Gy total body irradiation. Iterative sequencing and RT-PCR confirmation of 4 respiratory samples over the 4-week peritransplant period revealed that the pre-conditioning strain contained an intact ORF4 gene, while the deletion strain appeared just after conditioning and persisted over a 2.5-week period. This sequence represents one of the largest genomic deletions detected in a human RNA virus and is the first description of large-scale viral mutation associated with myeloablation for HCT.

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          Author and article information

          Journal
          bioRxiv
          March 03 2017
          Article
          10.1101/113423
          583c22df-067d-4790-adbe-d4f84a9142c0
          © 2017
          History

          Human biology,Genetics
          Human biology, Genetics

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