TY  - JOUR
AB  - 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-virusinduced 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.
AU  - Hafezi, Wali
AU  - Lorentzen, Eva U.
AU  - Eing, Bodo
AU  - Eing, Bodo R.
AU  - Müller, Marcus
AU  - King, Nicholas J. C.
AU  - Klupp, Barbara
AU  - Mettenleiter, Thomas C.
AU  - Kühn, Joachim
DA  - 2012-05-10
DO  - doi:10.1371/journal.ppat.1002679
LA  - eng
N1  - Finanziert durch den Open-Access-Publikationsfonds 2012/2013 der Deutschen Forschungsgemeinschaft (DFG) und der Westfälischen Wilhelms-Universität Münster (WWU Münster).
N1  - PLoS Pathogens 8 (2012) 5, e1002679
PY  - 2012-05-10
TI  - Entry of Herpes Simplex Virus Type 1 (HSV-1) into the Distal Axons of Trigeminal Neurons Favors the Onset of Nonproductive, Silent Infection
UR  - https://nbn-resolving.org/urn:nbn:de:hbz:6-47379611983
Y2  - 2024-11-21T21:20:30
ER  -