Nectin-1/HveC mediates herpes simplex virus type 1 entry into primary human sensory neurons and fibroblasts

Immunocytochemistry detects nectin-1/HveC, nectin-2/HveB, and HVEM/HveA on the surface of sensory neurons and fibroblasts grown as primary cultures from human dorsal root ganglia. Viral entry into these cultured cells was assayed by infection with a recombinant herpes simplex virus type 1 (HSV-1) expressing green fluorescent protein. Soluble, truncated nectin-1 polypeptide, as well as polyclonal and monoclonal antibodies against nectin-1, inhibited infection of neurons, whereas polypeptides and antibodies capable of inhibiting HSV-1 interaction with nectin-2 and herpesvirus entry mediator (HVEM) failed to prevent infection of neuronal cells. These results demonstrate that nectin-1 is the primary receptor for HSV-1 entry into human fetal neurons. Viral entry into fibroblasts was also reduced by soluble nectin-1 but not by soluble HVEM. However, in contrast to the results obtained with neurons, antibodies against receptors failed to inhibit entry into fibroblasts, indicating that unlike neurons, fibroblasts have multiple receptors or mechanisms for HSV-1 entry.