Host, Viral, and Environmental Transcriptome Profiles of the Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2)

Daniel J Butler; Christopher Mozsary; Cem Meydan; David C Danko; Jonathan Foox; Joel Rosiene; Alon Shaiber; Ebrahim Afshinnekoo; Matthew MacKay; Fritz J Sedlazeck; Nikolay A Ivanov; Maria A Sierra; Diana Pohle; Michael Zeitz; Vijendra Ramlall; Undina Gisladottir; Craig D Westover; Krista Ryon; Benjamin Young; Chandrima Bhattacharya; Phyllis Ruggiero; Bradley W Langhorst; Nathan A Tanner; Justyn Gawrys; Dmitry Meleshko; Dong Xu; Jenny Xiang; Angelika Iftner; Daniela Bezdan; John Sipley; Lin Cong; Arryn Craney; Priya Velu; Ari Melnick; Iman A Hajirasouliha; Thomas Iftner; Mirella Salvatore; Massimo Loda; Lars F Westblade; Shawn Levy; Melissa Cushing; Nicholas P Tatonetti; Marcin Imielinski; Hanna Rennert; Christopher Mason

The only indel across the 89 genetic variants detected across our full-length assemblies was a 9 bp in-frame deletion (p.141_143KSD) in the gene encoding non-structural protein 1 (NSP1). NSP1 is a putative SARS-CoV-2 virulence factor that is highly divergent across betacoronaviruses (Narayanan et al., 2015) . This deletion was found via assembly in two of 93 NYPH-WCM samples, and showed robust read support with near 100% variant allele fraction across hundreds of high-quality alignments (Figure 4c ). An identical deletion was observed in 14 other samples in the GISAID database, spanning samples from England, Iceland, and Canada. This included 12 samples that were labeled as part of clade A2a by Nextstrain (Figure 4c ). This deletion removes three amino acids, including a variant position (143Y>F) in comparison to the SARS-CoV genome (Figure 4d ). These residues occur in a conserved portion of the C-terminal region of NSP1, which has been linked to host chemokine dysregulation and translational inhibition in SARS-CoV (Narayanan et al., 2015) .