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. © 2012 hafezi et al.