FUNCTIONAL REGION-IV OF GLYCOPROTEIN-D FROM HERPES-SIMPLEX VIRUS MODULATES GLYCOPROTEIN BINDING TO THE HERPESVIRUS ENTRY MEDIATOR

Citation
Ah. Rux et al., FUNCTIONAL REGION-IV OF GLYCOPROTEIN-D FROM HERPES-SIMPLEX VIRUS MODULATES GLYCOPROTEIN BINDING TO THE HERPESVIRUS ENTRY MEDIATOR, Journal of virology, 72(9), 1998, pp. 7091-7098
Citations number
46
Categorie Soggetti
Virology
Journal title
ISSN journal
0022538X
Volume
72
Issue
9
Year of publication
1998
Pages
7091 - 7098
Database
ISI
SICI code
0022-538X(1998)72:9<7091:FROGFH>2.0.ZU;2-8
Abstract
Glycoprotein D (gD) of herpes simplex virus (HSV) is essential for vir us entry and has four functional regions (I to IV) important for this process. We previously showed that a truncated form of a functional re gion TV variant, gD1(Delta 290-299t), had an enhanced ability to block virus entry and to bind to the herpesvirus entry mediator (HveAt; for merly HVEMt), a cellular receptor for HSV, To explore this phenotype f urther, we examined other forms of go, especially ones with mutations in region IV. Variant proteins with deletions of amino acids between 2 77 and 300 (region IV), as well as truncated forms lacking C-terminal residues up to amino acid 275 of go, were able to block HSV entry into Vero cells 1 to 2 logs better than wild-type gD1(306t), In contrast, go truncated at residue 234 did not block virus entry into Vero cells. Using optical biosensor technology, we recently showed that gD1(Delta 290-299t) had a 100-fold-higher affinity for HveAt than gD1(306t) (3. 3 x 10(-8) M versus 3.2 x 10(-6) M), Here we found that the affinities of other region IV variants for HveAt were similar to that of gD1(Del ta 290-299t). Thus, the affinity data follow the same hierarchy as the blocking data. In each case, the higher affinity was due primarily to a faster k(on) rather than to a slower k(off). Therefore, once the gD t-HveAt complex formed, its stability was unaffected by mutations in o r near region IV. go truncated at residue 234 bound to HveAt with a lo wer affinity (2.0 x 10(-5) M) than did gD1(306t) due to a more rapid k (off). These data suggest that residues between 234 and 275 are import ant for maintaining stability of the gDt-HveAt complex and that functi onal region TV is important for modulating the binding of go to HveA, The binding properties of any gD1(234t)-receptor complex could account for the inability of this form of got to block HSV infection.