Low pH-induced conformational change in herpes simplex virus glycoprotein B.
Herpesviruses can enter host cells using pH-dependent endocytosis pathways in a cell-specific manner. Envelope glycoprotein B (gB) is conserved among all herpesviruses and is a critical component of the complex that mediates membrane fusion and entry. Here we demonstrate that mildly acidic pH triggers specific conformational changes in herpes simplex virus (HSV) gB. The antigenic structure of gB was specifically altered by exposure to low pH both in vitro and during entry into host cells. The oligomeric conformation of gB was altered at a similar pH range. Exposure to acid pH appeared to convert virion gB into a lower-order oligomer. The detected conformational changes were reversible, similar to those in other class III fusion proteins. Exposure of purified, recombinant gB to mildly acidic pH resulted in similar changes in conformation and caused gB to become more hydrophobic, suggesting that low pH directly affects gB. We propose that intracellular low pH induces alterations in gB conformation that, together with additional triggers such as receptor binding, are essential for virion-cell fusion during herpesviral entry by endocytosis.
1101 E. Marshall St., Room 6-038, P.O. Box 980678, Richmond, VA 23298-0678. anicola@vcu.edu.
Stephen J
SJ
Dollery
Mark G
MG
Delboy
Anthony V
AV
Nicola
D000818:Animals; D000956:Antigens, Viral / Q000737:chemistry / Q000276:immunology; D002522:Chlorocebus aethiops; D006863:Hydrogen-Ion Concentration; D011487:Protein Conformation; D055503:Protein Multimerization; D020836:Protein Structure, Quaternary; D014709:Vero Cells; D014759:Viral Envelope Proteins / Q000737:chemistry* / Q000276:immunology
D000956:Antigens, Viral; D014759:Viral Envelope Proteins; C040495:glycoprotein B, Simplexvirus