TY - JOUR T1 - Myeloablation-associated deletion of 0RF4 in a human coronavirus 229E infection JF - bioRxiv DO - 10.1101/113423 SP - 113423 AU - Alexander L. Greninger AU - Gregory Pepper AU - Ryan C. Shean AU - Anne Cent AU - Isabel Palileo AU - Jane M. Kuypers AU - Joshua T. Schiffer AU - Keith R. Jerome Y1 - 2017/01/01 UR - http://biorxiv.org/content/early/2017/03/03/113423.abstract N2 - 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 0RF4 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 0RF4 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. ER -