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

Differentially expressed host genes indicated a wide range of antiviral responses, including some a common interferon response across all ranges of viral levels (Figure 6b) . The host transcriptome that exhibited the greatest amount of DEGs were those with the highest viral titer. Notably, host epithelial cells showed an increase in angiotensin converting enzyme 2 (ACE2) expression (q-value=0.006), which is the SARS-CoV-2 cellular receptor (Hoffmann et al., 2020) . This critical gene for viral entry exhibited a dose-dependent expression concomitant with the higher levels of SARS-CoV-2 virus, along with IFI27 (Interferon Alpha Inducible Protein 27) and IFI6 (Interferon Alpha Inducible Protein 6) (Figure 6c ). Other interferon-related genes included IFIT1, an interferon-induced antiviral RNA-binding protein that specifically binds single-stranded RNA bearing a 5'-triphosphate group (PPP-RNA) and SHFL (Shiftless Antiviral Inhibitor of Ribosomal Frameshifting). The DEGs also included HERC6 (HECT Containing E3 Ubiquitin Protein Ligase Family Member 6), which aids Class I MHC-mediated antigen processing and Interferon-Stimulated Genes (ISG) (Figure 6c, 6d) , underscoring the impact of the virus on these cells' immune response (Oudshoorn et al., 2012 . Also, a subset of cytokines (CXCL10, CXCL11, CCL8) showed the highest spike of expression in the higher viral load subgroup (Supp. Figure 10) , matching previous results from animal models and infected cells (Blanco-Melo et al., 2020) .