Distinct Roles for Sialoside and Protein Receptors in Coronavirus Infection

Qing, Enya; Hantak, Michael; Perlman, Stanley; Gallagher, Tom

Viruses frequently begin infection by attaching to cellular sialic acids (61) . Such viruses include several CoVs, which attach to sialates via spike S1A domains (11, 12) , at low affinity (18) , but relatively high multivalent avidity (21, 41) . Atomic resolution structures of 9-O-acetylated sialic acid in complex with the human OC43-CoV S1A domain (18) as well as several sialosides in complex with the MERS-CoV S1A (54) have revealed architectures of CoV-sialate binding sites. Yet even with this detailed understanding, it is not clear whether sialic acids confer susceptibility to CoV infection on their own or whether proteinaceous CoV receptors are also required. In considering this question, we first focused on the murine MHV JHM-CoV strain. This strain can infect cells and mice that lack the proteinaceous MHV receptor, mCEACAM1a (27, 30, 32-35, 62, 63) . This strain is also unusually sensitive to proteolytic activation of spike-mediated membrane fusion (46) , and therefore, we hypothesized that a low-affinity cell binding event, conceivably to cellular sialoglycans, might be sufficient for subsequent JHM-CoV protease-triggered fusion activation and cell entry.