Epitopes described in "Delaying the expression of herpes simplex virus type 1 glycoprotein B (gB) to a true late gene alters neurovirulence and inhibits the gB-CD8+ T-cell response in the trigeminal ganglion."

Reference
Article Authors:Srividya Ramachandran; Katherine A Davoli; Michael B Yee; Robert L Hendricks; Paul R Kinchington
Article Title:Delaying the expression of herpes simplex virus type 1 glycoprotein B (gB) to a true late gene alters neurovirulence and inhibits the gB-CD8+ T-cell response in the trigeminal ganglion.
Reference Detail
Reference ID:1020827
Abstract:Following herpes simplex virus type 1 (HSV-1) ocular infection of C57BL/6 mice, activated CD8(+) T cells specific for an immunodominant epitope on HSV-1 glycoprotein B (gB-CD8 cells) establish a stable memory population in HSV-1 latently infected trigeminal ganglia (TG), whereas non-HSV-specific CD8(+) T cells are lost over time. The retention and activation of gB-CD8 cells appear to be influenced by persistent viral antigenic exposure within the latently infected TG. We hypothesized that the low-level expression of gB from its native promoter before viral DNA synthesis is critical for the retention and activation of gB-CD8 cells in the TG during HSV-1 latency and for their ability to block HSV-1 reactivation from latency. To test this, we created a recombinant HSV-1 in which gB is expressed only after viral DNA synthesis from the true late gC promoter (gCp-gB). Despite minor growth differences compared to its rescuant in infected corneas, gCp-gB was significantly growth impaired in the TG and produced a reduced latent genome load. The gCp-gB- and rescuant-infected mice mounted similar gB-CD8 effector responses, but the size and activation phenotypes of the memory gB-CD8 cells were diminished in gCp-gB latently infected TG, suggesting that the stimulation of gB-CD8 cells requires gB expression before viral DNA synthesis. Surprisingly, late gB expression did not compromise the capacity of gB-CD8 cells to inhibit HSV-1 reactivation from latency in ex vivo TG cultures, suggesting that gB-CD8 cells can block HSV-1 reactivation at a very late stage in the viral life cycle. These data have implications for designing better immunogens for vaccines to prevent HSV-1 reactivation.
Date:2010
Reference Type:Literature
PubMed ID:20573821
Journal:J Virol
Journal Volume:84
Article Pages:8811-20
Journal ISSN:1098-5514
Article Chemical List:Viral Envelope Proteins;glycoprotein B, Simplexvirus
Article MeSH List:Animals; CD8-Positive T-Lymphocytes(immunology; virology); Cercopithecus aethiops; Female; Gene Expression Regulation, Viral; Herpes Simplex(genetics; immunology; virology); Herpesvirus 1, Human(genetics; immunology; pathogenicity); Humans; Mice; Mice, Inbred C57BL; Trigeminal Ganglion(immunology; virology); Vero Cells; Viral Envelope Proteins(genetics; immunology); Virulence
Curation Last Updated:2014-10-03 22:13:03