We have studied the receptor-specific function of four linker-insertion mutants of @entity3307 glycoprotein D (gD) representing each of the functional regions of gD. We used biosensor analysis to measure binding of the gD mutants to the receptors @entity69511 ( @entity69511 ) and @entity22633 ( @entity22633 ). One of the mutants, gD(inverted Delta 34t), failed to bind HVEMt but showed essentially @entity164 ( @entity164 ) affinity for @entity22633 t. The receptor-binding kinetics and affinities of the other three gD mutants varied over a 1,000-fold range, but each mutant had the same affinity for both receptors. All of the mutants were functionally impaired in virus entry and cell fusion, and the levels of activity were strikingly similar in these two assays. gD(inverted @entity69512 )-containing virus was defective on @entity69511 -expressing cells but did enter @entity22633 -expressing cells to about 60% of @entity164 levels. This showed that the defect of this form of gD on @entity69511 -expressing cells was primarily one of binding and that this was separable from its later function in virus entry. gD(inverted Delta 243t) showed @entity164 binding affinity for both receptors, but virus containing this form of gD had a markedly reduced rate of entry, suggesting that gD(inverted Delta 243) is impaired in a postbinding step in the entry process. There was no correlation between gD mutant activity in fusion or virus entry and receptor-binding affinity. We conclude that gD functions in virus entry and cell fusion regardless of its receptor-binding kinetics and that as long as binding to a functional receptor occurs, entry will progress.

Function of XXXX gD mutants with different receptor-binding affinities in virus entry and fusion.

@entity22633 :: ('5818', 'Gene') :: ['nectin-1', 'HveC'] @entity69512 :: ('|DEL||34', 'DNAMutation') :: ['Delta 34'] @entity164 :: ('MESH:D017827', 'Disease') :: ['WT', 'wild-type'] @entity3307 :: ('10298', 'Species') :: ['herpes simplex virus type 1'] @entity69511 :: ('8764', 'Gene') :: ['HVEM', 'HveA']
@entity3307 :: (10298,Species) :: ['herpes simplex virus type 1']
