Herpes simplex virus type 1 glycoprotein L mutants that fail to promote trafficking of glycoprotein H and fail to function in fusion can induce binding of glycoprotein L-dependent anti-glycoprotein H antibodies.
The herpes simplex virus type 1 (HSV-1) glycoproteins H (gH) and L (gL) form a heterodimer and efficient expression of gH at the virion or cell surface is dependent upon gL. Five carboxy-terminal deletion mutants of gL were created and their ability to interact with and mediate cell-surface expression of gH, to promote binding of gL-dependent anti-gH antibodies and to contribute to cell fusion was analysed. All of the gL mutants bound gH, but only two mutants, containing the amino-terminal 161 or 168 aa of gL, mediated cell-surface expression of gH, and only gL161 and gL168 functioned in cell fusion. The binding of gL to gH, therefore, was not sufficient to ensure gH cell-surface expression and it was not possible to separate the gH-trafficking role of gL from gL function in fusion. Co-expression of gH with any gL mutant conferred binding of the anti-gH mAbs 53S and LP11. If the acquisition of 53S and LP11 binding to gH reflects a gL-induced conformational change, such a change is not sufficient to mediate trafficking of the gH-gL heterodimer.
Klyachkin
Yuri M
YM
University of Kentucky, Department of Microbiology, Immunology, and Molecular Genetics, 800 Rose Street, UKMC MS415, Lexington, KY 40536-0298, USA.
Stoops
Krista D
KD
University of Kentucky, Department of Microbiology, Immunology, and Molecular Genetics, 800 Rose Street, UKMC MS415, Lexington, KY 40536-0298, USA.
Geraghty
Robert J
RJ
University of Kentucky, Department of Microbiology, Immunology, and Molecular Genetics, 800 Rose Street, UKMC MS415, Lexington, KY 40536-0298, USA.
D000595:Amino Acid Sequence; D000818:Animals; D000911:Antibodies, Monoclonal / Q000276:immunology / Q000378:metabolism; D000914:Antibodies, Viral / Q000276:immunology / Q000378:metabolism*; D002459:Cell Fusion; D006224:Cricetinae; D019281:Dimerization; D015967:Gene Expression Regulation, Viral; D018259:Herpesvirus 1, Human / Q000378:metabolism; D008561:Membrane Fusion / Q000502:physiology*; D051379:Mice; D008969:Molecular Sequence Data; D009154:Mutation; D051381:Rats; D017384:Sequence Deletion; D014759:Viral Envelope Proteins / Q000737:chemistry / Q000235:genetics* / Q000276:immunology* / Q000378:metabolism*
D000911:Antibodies, Monoclonal; D000914:Antibodies, Viral; D014759:Viral Envelope Proteins; C044200:glycoprotein H, herpes simplex virus type 1; C077407:glycoprotein L, Human herpesvirus 1