The Early Expression of Glycoprotein B from Herpes Simplex Virus Can Be Detected by Antigen-Specific CD8⁺T Cells

Abstract

The immune response to cutaneous herpes simplex virus type 1 (HSV-1) infection begins with remarkable rapidity. Activation of specific cytotoxic T lymphocytes (CTL) begins within hours of infection, even though the response within the draining lymph nodes peaks nearly 5 days later. HSV gene products are classified into three main groups, ␣, ␤, and ␥, based on their kinetics and requirements for expression. In C57BL/6 mice, the immunodominant epitope from HSV is derived from glycoprotein B (gB 498-505 ). While gB is considered a ␥ or "late" gene product, previous reports have indicated that some level of gene expression may occur soon after infection. Using brefeldin A as a specific inhibitor of viral antigen presentation to major histocompatibility complex class I-restricted CTL, we have formally addressed the timing of gB peptide expression in an immunologically relevant manner following infection. Presentation of gB peptide detected by T-cell activation was first observed within 2 h of infection. Comparison with another viral epitope expressed early during infection, HSV-1 ribonucleotide reductase, demonstrated that gB is presented with the same kinetics as this classical early-gene product. Moreover, this rapidity of gB expression was further illustrated via rapid priming of naïve transgenic CD8 ؉ T cells in vivo after HSV-1 infection of mice. These results establish that gB is expressed rapidly following HSV-1 infection, at levels capable of effectively stimulating CD8 ؉ T cells.

In Vivo Ablation of CD11c-Positive Dendritic Cells Increases Susceptibility to Herpes Simplex Virus Type 1 Infection and Diminishes NK and T-Cell Responses

“…To gauge the effects of DC depletion on CD8 ϩ T-cell activation and subsequent commitment to the immune response to HSV-1, class I MHC tetramer analysis was performed. Staining with H-2K b /gB peptide tetrameric reagents is a highly sensitive technique enabling the enumeration and characterization of HSV-1-specific CD8 ϩ T cells during infection (23). Using this approach, we found significantly reduced levels of gB ϩ CD8 ϩ T cells on day 4 postinfection in both the draining popliteal lymph nodes ( Fig.…”

A Lentiviral Vector-Based, Herpes Simplex Virus 1 (HSV-1) Glycoprotein B Vaccine Affords Cross-Protection against HSV-1 and HSV-2 Genital Infections

“…The interserotype homology is 85% at amino acid level and, with the exception of the N and C-terminal regions, the secondary structure is also highly similar (6). As a consequence, HSV-1 and HSV-2 gB share several Band T-lymphocyte epitopes that induce cross-reactive NAb and CTL responses in both natural and experimental infections (35,51) and have allowed the development of cross-neutralizing antibodies (29).…”

“…Specific immune responses blocking gB1-NMHC-IIA interplay could therefore greatly reduce viral infectivity. (ii) gB1 induces strong humoral and cell-mediated immune responses (17,35). (iii) It contains "protective" cytotoxic-T-lymphocyte (CTL) epitopes that are preferentially recognized by asymptomatic subjects, are important to prevent recurrent diseases, and maintain HSV-1 in a latent state (12,45).…”

Identification of an immunodominant epitope in glycoproteins B and G of herpes simplex viruses (HSVs) using synthetic peptides as antigens in assay of antibodies to HSV in herpes simplex encephalitis patients

“…It is reported that antibodies in CSF against gB in HSV were detected earlier than antibodies to the other viral proteins, probably because of high immunogenicity of gB (Kahlon et al, 1987). One study demonstrated that gB is presented with the same kinetics as a classical early-gene product and it is the possibility that gB could be an effective target as HSV emerges from latent infection (Mueller et al, 2003). It has also been shown that the functional domains of gB involved in cell penetration and cell fusion, and the major antigenic domains are highly conserved in peripheral and CNS HSV isolates (Sivadon et al, 1998) therefore, variation in antibody response against this protein could be least suspected.…”