Myeloablation-associated deletion of ORF4 in a human coronavirus 229E infection. (December 2017)

• Record Type: Journal Article
• Authors: Greninger, Alexander; Pepper, Gregory; Shean, Ryan; Cent, Anne; Palileo, Isabel; Kuypers, Jane; Schiffer, Joshua; Jerome, Keith
• Is Part Of: Npj genomic medicine. Volume 2(2017)
• Page Start: 1
• Page End: 4
• Publication Date: 2017-12
• Subjects: Medical genetics -- Periodicals; Genomics -- Periodicals; 611.01816
• DOI: 10.1038/s41525-017-0033-4
• Languages: English
• ISSNs: 2056-7944

Abstract

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 four 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 describes large-scale viral mutation associated with myeloablation for HCT.