800.227.0627

Definition
Herpes simplex virus (HSV) is a lytic virus. Infection of cells with the HSV leads to a gradual inhibition of cell-specific protein synthesis and a concomitant increase in the rate of synthesis of virus-specific proteins and peptides. Several interactions between HSV proteins have been proposed as attractive targets for antiviral drug discovery.

Discovery
JP Vasilakos in 1993 used a short synthetic peptide representing amino acid residues 497-507 from HSV-1 glycoprotein B to induce Cytotoxic T cells. C57BL/6 mice were immunized with a single dose of a short synthetic peptide representing amino acid residues 497-507 from HSV-1 glycoprotein B. The CTL were CD8+ and H-2b restricted. They were capable of lysing target cells exogenously sensitized with peptide or endogenously processed glycoprotein B 1. Paradis H in 1991 identified a nonapeptide, HSV R2-(329-337), corresponding to the subunit 2 (R2) carboxyl terminus of HSV ribonucleotide reductases, specifically inhibits this enzyme activity 2. HSV envelope glycoproteins are the prime targets of adaptive antiviral immunity. Three overlapping peptides showed ability to stimulate immunity which cross-reacts with HSV-1 3.

Structural Characteristics
Sequence of HSV-1 Glycoprotein (gB) (497-507) is H-Thr-Ser-Ser-Ile-Glu-Phe-Ala-Arg-Leu-Gln-Phe-OH. This peptide represents a H-2Kb T cell epitope of HSV-1 gB. It activates CD8+ cytotoxic T lymphocytes in vivo in a manner independent of CD4+ T cells. HSV R2-(329-337) is a nine amino acid peptide, this peptide was rapidly degraded by proteases present in the partially purified enzyme extract. The main process of proteolysis involves the successive removal of Tyr329 and Ala330, which corresponds to an aminopeptidase activity 2.

Mode of action
CTL primed with peptide sequence 497-507 from HSV-1 glycoprotein B produce an anamnestic response in vivo upon peptide challenge. The requirement of CD4+ T cells for CD8+ CTL activation was shown by depleting CD4+ cells in vivo with GK1.5 mAb. CD4+ T cell depletion did not abrogate CTL generation. These results suggest that glycoprotein B peptide 497-507 activates CD8+ CTL in vivo in a manner independent of CD4+ T cells 1. Nx-acetylation, a modification known to protect nonapeptide, HSV R2-(329-337), against aminopeptidase attacks, greatly improved the proteolytic resistance of HSVs 2.

Two peptides, the gB 18-mer and 20.1-mer, were recognized by MAb B6 and HSV-immune antibody but were unable to stimulate virus-neutralizing antibody or serum able to protect against zosteriform spread in vivo. The 20.2-mer peptide, however, which was not recognized by MAb B6 or HSV-generated immune antibody, stimulated the production of neutralizing antibody and serum able to protect against zosteriform spread 3.

A synthetic peptide derived from the secreted portion of HSV type 2 glycoprotein G, denoted gG-2p20, which has proinflammatory properties in vitro. The gG-2p20 peptide, corresponding to aa 190–205 of glycoprotein G-2, was a chemoattractant for both monocytes and neutrophils in a dose-dependent fashion, and also induced the release of reactive oxygen from these cells. The receptor mediating the responses was identified as the formyl peptide receptor. The gG-2p20-induced activation of phagocytes had a profound impact on NK cell functions. The reactive oxygen species produced by gG-2p20-activated phagocytes both inhibited NK cell cytotoxicity and accelerated the apoptotic cell death in NK cell-enriched lymphocyte populations 4.

Functions

Cellular and humoral immunity,
investigation of the immune response to herpes simplex virus (HSV) has indicated that certain viral envelope glycoproteins, especially gB, gC, and gD, generate both cellular and humoral immunity 5,6.

Host cell entry, glycoproteins B and D, essential for virus entry into host cells, act as protective immunogens in animals when introduced in recombinant virus vectors, as purified proteins, or in transfected L cells 7.

Neutralizing antibody, three overlapping peptides, corresponding to the wild-type gB-1 sequence amino acids 63 to 110 have the ability to stimulate immunity in mice which cross-reacts with HSV-1. One peptide was able to generate HSV-1 neutralizing antibody which protected in the murine zosteriform spread model.

CCAP, the complex of native cytokines and antimicrobial peptides (CCAP or Superlymph) proved to inhibit the HSV reproduction in vitro. Protegrines, as a CCAP component, were active against the virus 8.

References

1.     Vasilakos JP, Michael JG (1993). Herpes simplex virus class I-restricted peptide induces cytotoxic T lymphocytes in vivo independent of CD4+ T cells. J. Immunol., 150(6):2346-2355.

2.     Paradis H, Langelier Y, Michaud J, Brazeau P, Gaudreau P (1991). Studies on in vitro proteolytic sensitivity of peptides inhibiting herpes simplex virus ribonucleotide reductases lead to discovery of a stable and potent inhibitor. Int J Pept Protein Res., 37(1):72-79.

3.     Mester JC, Highlander SL, Osmand AP, Glorioso JC, Rouse BT (1990). Herpes Simplex Virus Type 1-Specific Immunity Induced by Peptides Corresponding to an Antigenic Site of Glycoprotein B. J. Virology., 64(11):5277-5283.

4.     Bellner L (2005). A Proinflammatory Peptide from Herpes Simplex Virus Type 2 Glycoprotein G Affects Neutrophil, Monocyte, and NK Cell Functions. The Journal of Immunology, 174:2235-2241.

5.     Vestergaard BF (1980). Herpes simplex virus antigens and antibodies: a survey of studies based on quantitative immunoelectrophoresis. Rev. Infect. Dis., 2:899-913.

6.     Zarling JM (1986). T cell-mediated immunity to herpes simplex viruses, p. 103-114. In C. Lopez and B. Roizman (ed.), Human herpesvirus infections. Raven Press, New York.

7.     Corey L, Spear PG (1986). Infections with herpes simplex viruses. N. Engl. J. Med., 314: 686-691.

8.     Kovalchuk LV, Gankovskaya LV, Gankovskaya OA, Lavrov VF (2007). Herpes simplex virus: treatment with antimicrobial peptides. Adv Exp Med Biol., 601:369-376.

If you are unable to find your desired product please contact us for assistance or send an email to info@biosyn.com

 

Biosynthesis Inc.