The ectodomain of herpes simplex virus glycoprotein H contains a membrane alpha-helix with attributes of an internal fusion peptide, positionally conserved in the herpesviridae family.
Human herpesviruses enter cells by fusion with target membranes, a process that requires three conserved glycoproteins: gB, gH, and gL. How these glycoproteins execute fusion is unknown. Neural network bioinformatics predicted a membrane alpha-helix contained within the ectodomain of herpes simplex virus (HSV) gH, positionally conserved in the gH of all examined herpesviruses. Evidence that it has attributes of an internal fusion peptide rests on the following lines of evidence. (i) The predicted membrane alpha-helix has the attribute of a membrane segment, since it transformed a soluble form of gD into a membrane-bound gD. (ii) It represents a critical domain of gH. Its partial or entire deletion, or substitution of critical residues inhibited HSV infectivity and fusion in the cell-cell fusion assay. (iii) Its replacement with the fusion peptide from human immunodeficiency virus gp41 or from vesicular stomatitis virus G partially rescued HSV infectivity and cell-cell fusion. The corresponding antisense sequences did not. (iv) The predicted alpha-helix located in the varicella-zoster virus gH ectodomain can functionally substitute the native HSV gH membrane alpha-helix, suggesting a conserved function in the human herpesviruses. We conclude that HSV gH exhibits features typical of viral fusion glycoproteins and that this property is likely conserved in the Herpesviridae family.
Gianni
Tatiana
T
Department of Experimental Pathology, Section on Microbiology and Virology, University of Bologna, Via San Giacomo, 12, 40126 Bologna, Italy.
Martelli
Pier Luigi
PL
Casadio
Rita
R
Campadelli-Fiume
Gabriella
G
D000595:Amino Acid Sequence; D000818:Animals; D001483:Base Sequence; D019556:COS Cells; D002460:Cell Line; D017124:Conserved Sequence; D006224:Cricetinae; D004279:DNA, Viral / Q000235:genetics; D015700:HIV Envelope Protein gp41 / Q000737:chemistry / Q000235:genetics; D006564:Herpesviridae / Q000235:genetics; D018259:Herpesvirus 1, Human / Q000737:chemistry* / Q000235:genetics; D008562:Membrane Glycoproteins / Q000737:chemistry / Q000235:genetics; D008969:Molecular Sequence Data; D016296:Mutagenesis; D017433:Protein Structure, Secondary; D017434:Protein Structure, Tertiary; D011993:Recombinant Fusion Proteins / Q000737:chemistry / Q000235:genetics; D017384:Sequence Deletion; D014162:Transfection; D014759:Viral Envelope Proteins / Q000737:chemistry* / Q000235:genetics; D014760:Viral Fusion Proteins / Q000737:chemistry / Q000235:genetics; D014764:Viral Proteins / Q000737:chemistry / Q000235:genetics
D004279:DNA, Viral; D015700:HIV Envelope Protein gp41; D008562:Membrane Glycoproteins; D011993:Recombinant Fusion Proteins; D014759:Viral Envelope Proteins; D014760:Viral Fusion Proteins; D014764:Viral Proteins; C044200:glycoprotein H, herpes simplex virus type 1; C040496:gp 118 protein, Herpesvirus 3, Human