Upregulation of Multiple CD8 T Cell Exhaustion Pathways Is Associated with Recurrent Ocular Herpes Simplex Virus Type 1 Infection.

A large proportion of the world's population harbors latent HSV type 1 (HSV-1). Cross-talk between antiviral CD8 T cells and HSV-1 appear to control latency/reactivation cycles. We found that compared with healthy asymptomatic individuals, in symptomatic (SYMP) patients, the CD8 T cells with the same HLA-A*0201-restricted HSV-1 epitope specificities expressed multiple genes and proteins associated to major T cell exhaustion pathways and were dysfunctional.

High Frequency of Gamma Interferon-Producing PLZFRORγt Invariant Natural Killer 1 Cells Infiltrating Herpes Simplex Virus 1-Infected Corneas Is Associated with Asymptomatic Ocular Herpesvirus Infection.

Invariant natural killer (iNKT) cells are among the first innate immune cells to elicit early protective immunity that controls invading viral pathogens. The role of the iNKT cell subsets iNKT1, iNKT2, and iNKT17 in herpesvirus immunity remains to be fully elucidated. In this study, we examined the protective role of cornea-resident iNKT cell subsets using the mouse model of ocular herpesvirus infection and disease.

Human Epitopes Identified from Herpes Simplex Virus Tegument Protein VP11/12 (UL46) Recall Multifunctional Effector Memory CD4 T Cells in Asymptomatic Individuals and Protect from Ocular Herpes Infection and Disease in "Humanized" HLA-DR Transgenic Mice.

While the role of CD8 T cells in the control of herpes simplex virus 1 (HSV-1) infection and disease is gaining wider acceptance, a direct involvement of effector CD4 T cells in this protection and the phenotype and function of HSV-specific human CD4 T cell epitopes remain to be fully elucidated. In the present study, we report that several epitopes from the HSV-1 virion tegument protein (VP11/12) encoded by UL46 are targeted by CD4 T cells from HSV-seropositive asymptomatic individuals (who, despite being infected, never develop any recurrent herpetic disease). Among these, we identified two immunodominant effector memory CD4 T cell epitopes, amino acids (aa) 129 to 143 of VP11/12 (VP11/12) and VP11/12, using , , and approaches based on the following: (i) a combination of the TEPITOPE algorithm and PepScan library scanning of the entire 718 aa of HSV-1 VP11/12 sequence; (ii) an peptide-protein docking analysis and binding assay that identify epitopes with high affinity to soluble HLA-DRB1 molecules; and (iii) an ELISpot assay and intracellular detection of gamma interferon (IFN-γ), CD107 degranulation, and CD4 T cell carboxyfluorescein succinimidyl ester (CFSE) proliferation assays.

NLRP3, NLRP12, and IFI16 Inflammasomes Induction and Caspase-1 Activation Triggered by Virulent HSV-1 Strains Are Associated With Severe Corneal Inflammatory Herpetic Disease.

The crosstalk between the host's inflammasome system and the invading virulent/less-virulent viruses determines the outcome of the ensuing inflammatory response. An appropriate activation of inflammasomes triggers antiviral inflammatory responses that clear the virus and heal the inflamed tissue. However, an aberrant activation of inflammasomes can result in a harmful and overwhelming inflammation that could damage the infected tissue.