title: Glycoprotein B of herpes simplex virus 2 has more than one intracellular conformation and is altered by low pH.
abstract: The crystal structure of herpes simplex virus (HSV) gB identifies it as a class III fusion protein, and comparison with other such proteins suggests this is the postfusion rather than prefusion conformation, although this is not proven. Other class III proteins undergo a pH-dependent switch between pre- and postfusion conformations, and a low pH requirement for HSV entry into some cell types suggests that this may also be true for gB. Both gB and gH undergo structural changes at low pH, but there is debate about the extent and significance of the changes in gB, possibly due to the use of different soluble forms of the protein and different assays for antigenic changes. In this study, a complementary approach was taken, examining the conformations of full-length intracellular gB by quantitative confocal microscopy with a panel of 26 antibodies. Three conformations were distinguished, and low pH was found to be a major influence. Comparison with previous studies indicates that the intracellular conformation in low-pH environments may be the same as that of the soluble form known as s-gB at low pH. Interestingly, the antibodies whose binding was most affected by low pH both have neutralizing activity and consequently must block either the function of a neutral pH conformation or its switch from an inactive form to an activated form. If one of the intracellular conformations is the fusion-active form, another factor required for fusion is presumably absent from wherever that conformation is present in infected cells so that inappropriate fusion is avoided.
authors.affiliation: Center for Molecular and Tumor Virology, Department of Microbiology and Immunology, and Feist-Weiller Cancer Center, Louisiana State University Health Sciences Center, Shreveport, Louisiana 71130, USA.
authors.forename: Martin I
authors.initials: MI
authors.lastname: Muggeridge
mesh_terms: D000818:Animals; D006558:Herpes Genitalis / Q000821:virology*; D018258:Herpesvirus 2, Human / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D006863:Hydrogen-Ion Concentration; D011487:Protein Conformation; D014759:Viral Envelope Proteins / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism
chemical_list: D014759:Viral Envelope Proteins; C044525:glycoprotein B, herpes simplex virus type 2