T cell immunity in HSV-1- and VZV-infected neural ganglia

Herpesviruses exert a multitude of MHC class I (MHC I) and class II (MHC II) immune evasion strategies to establish persistent infections. A newly described mechanism involves epitope evasion through depletion of high-affinity peptides that fit into the MHC I binding cleft. MHC I and MHC II molecules are also expressed in the 'immune-privileged' nervous system. T cell immunity plays an active but not fully understood role in the nervous system to prevent herpes simplex virus-1 (HSV-1) and varicella-zoster virus (VZV) reactivation. CD8+ T cells can control viral infection without causing neuronal cell death via (i) nonlytic cytokines, such as interferon-y, and/or (ii) via lytic granules such as granzyme B that degrade specific viral proteins. Neuronal HSV-1 infection seems to be mainly controlled by CD8+ T cells through noncytolytic mechanisms, while VZV seems to be largely controlled through CD4+ T cell-specific immune responses. Herpesviruses hijack the MHC class I (MHC I) and class II (MHC II) antigen-presentation pathways to manipulate immune recognition by T cells. First, we illustrate herpes simplex virus-1 (HSV-1) and varicella-zoster virus (VZV) MHC immune evasion strategies. Next, we describe MHC–T cell interactions in HSV-1- and VZV- infected neural ganglia. Although studies on the topic are scarce, and use different models, most reports indicate that neuronal HSV-1 infection is mainly controlled by CD8+ T cells through noncytolytic mechanisms, whereas VZV seems to be largely controlled through CD4+ T cell-specific immune responses. Autologous human stem-cell-derived in vitro models could substantially aid in elucidating these neuroimmune interactions and are fit for studies on both herpesviruses. Herpesviruses hijack the MHC class I (MHC I) and class II (MHC II) antigen-presentation pathways to manipulate immune recognition by T cells. First, we illustrate herpes simplex virus-1 (HSV-1) and varicella-zoster virus (VZV) MHC immune evasion strategies. Next, we describe MHC–T cell interactions in HSV-1- and VZV- infected neural ganglia. Although studies on the topic are scarce, and use different models, most reports indicate that neuronal HSV-1 infection is mainly controlled by CD8+ T cells through noncytolytic mechanisms, whereas VZV seems to be largely controlled through CD4+ T cell-specific immune responses. Autologous human stem-cell-derived in vitro models could substantially aid in elucidating these neuroimmune interactions and are fit for studies on both herpesviruses.