(A) Summary table of SARS-CoV-2 (CoV-2) Orf3aHALO colocalization with subcellular protein markers. All markers used to identify cellular compartments are listed in the table in A and are transiently expressed (mEm, mEmerald; mNG, mNeonGreen; GFP, green fluorescent protein). (B) Live-cell image of transiently expressed farnesylated-GFP (green) and CoV-2 Orf3aHALO (magenta) using a HEK293 doxycycline-inducible CoV-2 Orf3aHALO stable cell line. White arrows indicate co-localization. (C) Total Internal Reflection Fluorescence (TIRF) imaging of HEK293 cell with transient expression of CoV-2 Orf3aHALO (white). Orange box, magnification of the surface to highlight CoV-2 Orf3aHALO (black). (D–I) Live-cell image of transiently expressed (D) Rab5-mEm, (E) Rab7-mEm, (F) LAMP1-mEm, (G) Sec61-mEm, (H) αMannosidase-II-mEm, or (I) Pex11-mNG (green) with CoV-2 Orf3aHALO (magenta) as described in (B). White boxes indicate regions of co-localization. All confocal images are representative of three to six independent experiments.