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

By Alexander Greninger, Gregory Pepper, Ryan C Shean, Anne Cent, Isabel Palileo, Jane M. Kuypers, Joshua T Schiffer, Keith R Jerome

Posted 03 Mar 2017
bioRxiv DOI: 10.1101/113423 (published DOI: 10.1038/s41525-017-0033-4)

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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