PMID- 19168902
OWN - NLM
STAT- MEDLINE
DCOM- 20090611
LR  - 20231213
IS  - 1552-5783 (Electronic)
IS  - 0146-0404 (Linking)
VI  - 50
IP  - 6
DP  - 2009 Jun
TI  - The role of a glycoprotein K (gK) CD8+ T-cell epitope of herpes simplex virus on 
      virus replication and pathogenicity.
PG  - 2903-12
LID - 10.1167/iovs.08-2957 [doi]
AB  - 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.
FAU - Mott, Kevin R
AU  - Mott KR
AD  - Center for Neurobiology and Vaccine Development, Ophthalmology Research, 
      Cedars-Sinai Medical Center Burns and Allen Research Institute, Los Angeles, 
      California 90048, USA.
FAU - Chentoufi, Aziz A
AU  - Chentoufi AA
FAU - Carpenter, Dale
AU  - Carpenter D
FAU - BenMohamed, Lbachir
AU  - BenMohamed L
FAU - Wechsler, Steven L
AU  - Wechsler SL
FAU - Ghiasi, Homayon
AU  - Ghiasi H
LA  - eng
GR  - EY13615/EY/NEI NIH HHS/United States
GR  - R01 EY019896/EY/NEI NIH HHS/United States
GR  - R03 EY014017/EY/NEI NIH HHS/United States
GR  - R01 EY014900/EY/NEI NIH HHS/United States
GR  - R01 EY024618/EY/NEI NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
DEP - 20090124
PL  - United States
TA  - Invest Ophthalmol Vis Sci
JT  - Investigative ophthalmology & visual science
JID - 7703701
RN  - 0 (Epitopes, T-Lymphocyte)
RN  - 0 (Lamp1 protein, mouse)
RN  - 0 (Lysosomal Membrane Proteins)
RN  - 0 (Ophthalmic Solutions)
RN  - 0 (Peptide Fragments)
RN  - 0 (UL53 protein, Human herpesvirus 1)
RN  - 0 (Viral Proteins)
RN  - 82115-62-6 (Interferon-gamma)
SB  - IM
MH  - Animals
MH  - CD8-Positive T-Lymphocytes/*immunology
MH  - Cornea/virology
MH  - Cytotoxicity, Immunologic
MH  - Disease Models, Animal
MH  - Enzyme-Linked Immunosorbent Assay
MH  - Epitopes, T-Lymphocyte/*immunology
MH  - Female
MH  - Herpesvirus 1, Human/*pathogenicity/*physiology
MH  - Immunization
MH  - Interferon-gamma
MH  - Keratitis, Herpetic/immunology/*virology
MH  - Lysosomal Membrane Proteins
MH  - Mice
MH  - Mice, Inbred BALB C
MH  - Mice, Inbred C57BL
MH  - Ophthalmic Solutions
MH  - Peptide Fragments/administration & dosage
MH  - Rabbits
MH  - Reverse Transcriptase Polymerase Chain Reaction
MH  - Viral Proteins/*immunology
MH  - Virus Replication/*physiology
EDAT- 2009/01/27 09:00
MHDA- 2009/06/12 09:00
CRDT- 2009/01/27 09:00
PHST- 2009/01/27 09:00 [entrez]
PHST- 2009/01/27 09:00 [pubmed]
PHST- 2009/06/12 09:00 [medline]
AID - iovs.08-2957 [pii]
AID - 10.1167/iovs.08-2957 [doi]
PST - ppublish
SO  - Invest Ophthalmol Vis Sci. 2009 Jun;50(6):2903-12. doi: 10.1167/iovs.08-2957. 
      Epub 2009 Jan 24.