Reversible conformational change in herpes simplex virus glycoprotein B with fusion-from-without activity is triggered by mildly acidic pH.
BACKGROUND
The pre-fusion form of the herpes simplex virus (HSV) fusion protein gB undergoes pH-triggered conformational change in vitro and during viral entry (Dollery et al., J. Virol. 84:3759-3766, 2010). The antigenic structure of gB from the fusion-from-without (FFWO) strain of HSV-1, ANG path, resembles wild type gB that has undergone pH-triggered changes. Together, changes in the antigenic and oligomeric conformation of gB correlate with fusion activity. We tested whether the pre-fusion form of FFWO gB undergoes altered conformational change in response to low pH.


RESULTS
A pH of 5.5 - 6.0 altered the conformation of Domains I and V of FFWO gB, which together comprise the functional region containing the hydrophobic fusion loops. The ANG path gB oligomer was altered at a similar pH. All changes were reversible. In wild type HSV lacking the UL45 protein, which has been implicated in gB-mediated fusion, gB still underwent pH-triggered changes. ANG path entry was inactivated by pretreatment of virions with low pH.


CONCLUSIONS
The pre-fusion conformation of gB with enhanced fusion activity undergoes alteration in antigenic structure and oligomeric conformation in response to acidic pH. We propose that endosomal pH triggers conformational change in mutant gB with FFWO activity in a manner similar to wild type. Differences apart from this trigger may account for the increased fusion activity of FFWO gB.
Department of Microbiology and Immunology, Virginia Commonwealth University School of Medicine, 1101 East Marshall Street, Richmond, Virginia 23298-0678, USA.
Carlos R
CR
Siekavizza-Robles
Stephen J
SJ
Dollery
Anthony V
AV
Nicola
D000818:Animals; D000956:Antigens, Viral / Q000737:chemistry* / Q000378:metabolism*; D002522:Chlorocebus aethiops; D018259:Herpesvirus 1, Human / Q000737:chemistry* / Q000502:physiology; D006863:Hydrogen-Ion Concentration; D011487:Protein Conformation / Q000187:drug effects; D055503:Protein Multimerization; D014709:Vero Cells; D014759:Viral Envelope Proteins / Q000737:chemistry* / Q000378:metabolism*
D000956:Antigens, Viral; D014759:Viral Envelope Proteins; C040495:glycoprotein B, Simplexvirus