Fibril Formation and Neurotoxicity by a Herpes Simplex Virus Glycoprotein B Fragment with Homology to the Alzheimer's Aβ Peptide†

Biochemistry ◽  
2000 ◽  
Vol 39 (20) ◽  
pp. 5988-5994 ◽  
Author(s):  
David H. Cribbs ◽  
Bassem Y. Azizeh ◽  
Carl W. Cotman ◽  
Frank M. LaFerla
Keyword(s):  
Herpes Simplex Virus ◽  
Herpes Simplex ◽  
Fibril Formation ◽  
Glycoprotein B ◽  
Aβ Peptide ◽  
Virus Glycoprotein ◽  
Herpes Simplex Virus Glycoprotein ◽  
Simplex Virus

scholarly journals Mutational Evidence of Internal Fusion Loops in Herpes Simplex Virus Glycoprotein B

2007 ◽  
Vol 81 (9) ◽  
pp. 4858-4865 ◽  
Author(s):  
Brian P. Hannah ◽  
Ekaterina E. Heldwein ◽  
Florent C. Bender ◽  
Gary H. Cohen ◽  
Roselyn J. Eisenberg
Keyword(s):  
Amino Acids ◽  
Herpes Simplex Virus ◽  
Herpes Simplex ◽  
Fusion Proteins ◽  
Glycoprotein B ◽  
Functional Domain ◽  
Virus Glycoprotein ◽  
Herpes Simplex Virus Glycoprotein ◽  
Simplex Virus ◽  
Hsv 1

ABSTRACT Herpes simplex virus type 1 (HSV-1) glycoprotein B (gB) is one of four glycoproteins necessary and sufficient for HSV cellular entry. Recently, the crystal structures of HSV-1 gB and vesicular stomatitis virus glycoprotein G were determined. Surprisingly, the two proteins share remarkable structural homology. Both proteins are homotrimeric and center about a long alpha-helix, features reminiscent of class I fusion proteins, such as influenza virus hemagglutinin or paramyxovirus F. However, these structures revealed that G has internal fusion loops, similar to the fusion loops of the class II fusion proteins, and that these loops are structurally conserved in gB. To examine whether these putative fusion loops are important for gB function, we mutated potential membrane-interacting (hydrophobic) residues to charged amino acids. Of most interest were mutant gB proteins that were expressed on the cell surface and were recognized by monoclonal antibodies against conformational epitopes but lacked the ability to function in cell-cell fusion assays. We find that three of the five hydrophobic amino acids targeted in these loops, tryptophan 174, tyrosine 179, and alanine 261, are integral in the function of gB. Our data suggest that they are part of an important functional domain. We hypothesize that two loops in domain 1 of HSV gB function as fusion loops. Our data are further evidence that gB is a viral fusogen and suggest clues as to how gB may function.

scholarly journals The prefusion structure of herpes simplex virus glycoprotein B

2020 ◽  
Vol 6 (39) ◽  
pp. eabc1726 ◽  
Author(s):  
B. Vollmer ◽  
V. Pražák ◽  
D. Vasishtan ◽  
E. E. Jefferys ◽  
A. Hernandez-Duran ◽  
...  
Keyword(s):  
Herpes Simplex Virus ◽  
Herpes Simplex ◽  
Glycoprotein B ◽  
Viral Fusion ◽  
Class Iii ◽  
Virus Glycoprotein ◽  
Conserved Sequence ◽  
Herpes Simplex Virus Glycoprotein ◽  
Simplex Virus ◽  
Hsv 1

Cell entry of enveloped viruses requires specialized viral proteins that mediate fusion with the host membrane by substantial structural rearrangements from a metastable pre- to a stable postfusion conformation. This metastability renders the herpes simplex virus 1 (HSV-1) fusion glycoprotein B (gB) highly unstable such that it readily converts into the postfusion form, thereby precluding structural elucidation of the pharmacologically relevant prefusion conformation. By identification of conserved sequence signatures and molecular dynamics simulations, we devised a mutation that stabilized this form. Functionally locking gB allowed the structural determination of its membrane-embedded prefusion conformation at sub-nanometer resolution and enabled the unambiguous fit of all ectodomains. The resulting pseudo-atomic model reveals a notable conservation of conformational domain rearrangements during fusion between HSV-1 gB and the vesicular stomatitis virus glycoprotein G, despite their very distant phylogeny. In combination with our comparative sequence-structure analysis, these findings suggest common fusogenic domain rearrangements in all class III viral fusion proteins.

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