Here, we generated A549 single-cell CRISPR/Cas9 knockout clones of desmoglein 2 (DSG2), CD46, the coxsackievirus and adenovirus receptor (CAR), and cytidine monophosphate N-acetylneuraminic acid synthetase (CMAS; needed for biosynthesis of sialic acid-containing glycans), and assessed their relative importance for infection by 18 different HAdV-D types. The gene discussed is DSG2; the disease is infection.