Epitopes described in "The role of a glycoprotein K (gK) CD8+ T-cell epitope of herpes simplex virus on virus replication and pathogenicity."

Article Authors:Kevin R Mott; Aziz A Chentoufi; Dale Carpenter; Lbachir BenMohamed; Steven L Wechsler; Homayon Ghiasi
Article Title:The role of a glycoprotein K (gK) CD8+ T-cell epitope of herpes simplex virus on virus replication and pathogenicity.
Reference Detail
Reference ID:1014902
Abstract:PURPOSE: The authors recently reported that a recombinant HSV-1 expressing two extra copies of glycoprotein K (gK) exacerbated corneal scarring (CS) in mice. The authors also identified a peptide, STVVLITAYGLVLVW, within the signal sequence of gK as an immunodominant gK T-cell-stimulatory region both in vitro and in vivo and identified a highly conserved potential CD8(+) T-cell epitope (ITAYGLVL) within the peptide. In this study, the effect of giving this octamer (8mer) as an eye drop 1 hour before ocular infection with HSV-1 was investigated. METHODS: Naive mice and rabbits received the gK 8mer or control peptides as eye drops and were then ocularly infected with HSV-1. Virus replication in the eye and trigeminal ganglia (TG), survival, CS, and relative amounts of gB, gK, CD4, CD8, IFN-gamma, and granzyme A/B transcripts were determined in the cornea and TG of infected animals at various times after infection. The effect of the gK 8mer was also analyzed in immunized HLA transgenic mice. RESULTS: The gK 8mer resulted in a short-term significant increase in virus replication in the eyes of BALB/c mice, C57BL/6 mice, and NZW rabbits. gK 8mer treatment also increased viral neurovirulence and viral induced CS in ocularly infected mice. Moreover, in HSV-infected humanized HLA-A*0201 transgenic mice, the gK 8mer epitope induced strong IFN-gamma-producing cytotoxic CD8(+) T-cell responses, as assessed by CD107a/b expression and IFN-gamma ELISAs. CONCLUSIONS: gK 8mer induced CD8(+) T-cell responses were unlikely to occur soon enough to account for increased virus replication on day 1 after infection. In contrast, the data are consistent with CD8(+) T cells being involved in the appearance of CS at late times after infection. In addition, the gK peptide may affect viral replication and innate immune responses through other undefined mechanisms.
Affiliations:Center for Neurobiology and Vaccine Development, Ophthalmology Research, Cedars-Sinai Medical Center Burns and Allen Research Institute, Los Angeles, California 90048, USA.
Reference Type:Literature
PubMed ID:19168902
Journal:Invest Ophthalmol Vis Sci
Journal Volume:50
Article Pages:2903-12
Journal ISSN:1552-5783
Article Chemical List:Epitopes, T-Lymphocyte;Lamp1 protein, mouse;Lysosome-Associated Membrane Glycoproteins;Ophthalmic Solutions;Peptide Fragments;UL53 protein, Human herpesvirus 1;Viral Proteins;Interferon-gamma
Article MeSH List:Animals; CD8-Positive T-Lymphocytes(immunology); Cornea(virology); Cytotoxicity, Immunologic; Disease Models, Animal; Enzyme-Linked Immunosorbent Assay; Epitopes, T-Lymphocyte(immunology); Female; Herpesvirus 1, Human(pathogenicity; physiology); Immunization; Interferon-gamma; Keratitis, Herpetic(immunology; virology); Lysosome-Associated Membrane Glycoproteins; Mice; Mice, Inbred BALB C; Mice, Inbred C57BL; Ophthalmic Solutions; Peptide Fragments(administration & dosage); Rabbits; Reverse Transcriptase Polymerase Chain Reaction; Viral Proteins(immunology); Virus Replication(physiology)
Curation Last Updated:2014-10-03 21:34:28