Entry of Herpes Simplex Virus Type 1 (HSV-1) into the Distal Axons of Trigeminal Neurons Favors the Onset of Nonproductive, Silent Infection

Following productive, lytic infection in epithelia, herpes simplex virus type 1 (HSV-1) establishes a lifelong latent infection in sensory neurons that is interrupted by episodes of reactivation. In order to better understand what triggers this lytic/latent decision in neurons, we set up an organotypic model based on chicken embryonic trigeminal ganglia explants (TGEs) in a double chamber system. Adding HSV-1 to the ganglion compartment (GC) resulted in a productive infection in the explants. By contrast, selective application of the virus to distal axons led to a largely nonproductive infection that was characterized by the poor expression of lytic genes and the presence of high levels of the 2.0-kb major latency-associated transcript (LAT) RNA. Treatment of the explants with the immediate-early (IE) gene transcriptional inducer hexamethylene bisacetamide, and simultaneous co-infection of the GC with HSV-1, herpes simplex virus type 2 (HSV-2) or pseudorabies virus (PrV) helper virus significantly enhanced the ability of HSV-1 to productively infect sensory neurons upon axonal entry. Helper-virus-induced transactivation of HSV-1 IE gene expression in axonally-infected TGEs in the absence of de novo protein synthesis was dependent on the presence of functional tegument protein VP16 in HSV-1 helper virus particles. After the establishment of a LAT-positive silent infection in TGEs, HSV-1 was refractory to transactivation by superinfection of the GC with HSV-1 but not with HSV-2 and PrV helper virus. In conclusion, the site of entry appears to be a critical determinant in the lytic/latent decision in sensory neurons. HSV-1 entry into distal axons results in an insufficient transactivation of IE gene expression and favors the establishment of a nonproductive, silent infection in trigeminal neurons

Single-channel EEG measurement of engagement in virtual rehabilitation: a validation study

Stroke rehabilitation suffers from low levels of patient engagement, impeding recovery. Virtual rehabilitation (VR) approaches can improve patient outcomes; however, there is limited understanding of the participant’s user experience and the field lacks a validated, objective measure of VR engagement. A neurophysiological measure of engagement in healthy adults was therefore examined, to inform future clinical studies. Twenty-four participants (Mage 26.7 years, range 18–47) interacted with a tabletop VR system (Elements DNA, or EDNA), after which they rated their experience on the presence questionnaire (PQ). Separately, participants completed tasks eliciting low (resting eyes-open and -closed) and high (EDNA VR and roller coaster simulation) levels of engagement while continuous electroencephalogram (EEG) was recorded from a single, left pre-frontal electrode. EEG differences between the resting and simulation conditions included an increase in theta power (p \u3c 0.01) and a decrease in alpha power (p \u3c 0.01). Importantly, theta power in simulation conditions correlated with PQ scores expressing the hands-on EDNA VR experience (rs = 0.38–0.48). In conclusion, the current results provide proof of concept that increased frontal theta power in healthy adults provides a valid measure of user engagement in VR simulation and participation. As the practical potential of VR is increasingly realised in stroke rehabilitation, objective EEG-based measures of engagement may provide a convenient and sensitive technique to assist in evaluating these interventions