Novel mutations in gB and gH circumvent the requirement for known gD Receptors in herpes simplex virus 1 entry and cell-to-cell spread.
J Virol
; 87(3): 1430-42, 2013 Feb.
Article
in En
| MEDLINE
| ID: mdl-23152509
ABSTRACT
Both entry and cell-to-cell spread of herpes simplex virus (HSV) involve a cascade of cooperative interactions among the essential glycoproteins D, B, and H/L (gD, gB, and gH/gL, respectively) initiated by the binding of gD to a cognate HSV entry receptor. We previously reported that a variant (D285N/A549T) of glycoprotein B (gBNT) enabled primary virus entry into cells that were devoid of typical HSV entry receptors. Here, we compared the activities of the gBNT variant with those of a newly selected variant of glycoprotein H (gHKV) and a frequently coselected gB variant (gBS668N). In combination, gHKV and gBS668N enabled primary virus entry into cells that lacked established HSV entry receptors as efficiently as did gBNT, but separately, each variant enabled only limited entry. Remarkably, gHKV uniquely facilitated secondary virus spread between cells that lacked canonical entry receptors. Transient expression of the four essential entry glycoproteins revealed that gHKV, but not gBNT, induced fusion between cells lacking the standard receptors. Because the involvement of gD remained essential for virus spread and cell fusion, we propose that gHKV mimics a transition state of gH that responds efficiently to weak signals from gD to reach the active state. Computational modeling of the structures of wild-type gH and gHKV revealed relatively subtle differences that may have accounted for our experimental findings. Our study shows that (i) the dependence of HSV-1 entry and spread on specific gD receptors can be reduced by sequence changes in the downstream effectors gB and gH, and (ii) the relative roles of gB and gH are different in entry and spread.
Full text:
1
Database:
MEDLINE
Main subject:
Viral Envelope Proteins
/
Herpesvirus 1, Human
/
Virus Internalization
Type of study:
Prognostic_studies
Limits:
Animals
/
Humans
Language:
En
Year:
2013
Type:
Article