Abstract
Herpes simplex virus type 1 (HSV-1) is a prevalent human pathogen. HSV-1 genomes persist in trigeminal ganglia neuronal nuclei as chromatinized episomes, while epithelial cells are typically killed by lytic infection. Fluctuations in anti-viral responses, broadly defined, may underlay periodic reactivations. The ganglionic immune response to HSV-1 infection includes cell-intrinsic responses in neurons, innate sensing by several cell types, and the infiltration and persistence of antigen-specific T-cells. The mechanisms specifying the contrasting fates of HSV-1 in neurons and epithelial cells may include differential genome silencing and chromatinization, dictated by variation in access of immune modulating viral tegument proteins to the cell body, and protection of neurons by autophagy. Innate responses have the capacity of recruiting additional immune cells and paracrine activity on parenchymal cells, for example via chemokines and type I interferons. In both mice and humans, HSV-1-specific CD8 and CD4 T-cells are recruited to ganglia, with mechanistic studies suggesting active roles in immune surveillance and control of reactivation. In this review we focus mainly on HSV-1 and the TG, comparing and contrasting where possible observational, interventional, and in vitro studies between humans and animal hosts.
Highlights
Herpes simplex virus type 1 (HSV-1), a human neurotropic alphaherpesvirus, is a prevalent human pathogen with a global cumulative burden of 3.7 billion infections [1]
The experimental HSV-1 rodent models have been a boon to dissecting these, and the development of human neuron models is allowing the knowledge learned from mice to be applied to humans
It is well established that data obtained in rodent models do not fully recapitulate the aspects of latency and reactivation of HSV-1 in its natural host
Summary
Herpes simplex virus type 1 (HSV-1), a human neurotropic alphaherpesvirus, is a prevalent human pathogen with a global cumulative burden of 3.7 billion infections [1]. Adult primary HSV-1 infection is recognized in the sexual transmitted infection literature in more than half of clinical first episodes of genital herpes in the US and areas of Europe [3] This is related, likely causally, to decreasing childhood prevalence with more persons initiating sexual activity when seronegative. Guinea pigs infected genitally with HSV-1 can have sporadic clinical and virologic recurrence after clearance of the inoculum that are thought associated with ganglionic reactivation [17] Control of HSV-1 acute infection, latency and reactivation in the ganglia occurs at many levels ranging from epigenetic modifications of histones near critical viral gene promoters to infiltration and retention of virus-specific T-cells. Recommendations are made to facilitate convergence towards in vitro and in vivo model systems and defined reagents with the goal of facilitating interlaboratory interpretation of research findings and progress in reducing the clinical consequences of latent ganglionic HSV-1 infection
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