|169-1||HERPES SIMPLEX VIRUS TYPE 1 INFECTION ALTERS EXPRESSION OF THE NEURONAL PLASTICITY-ASSOCIATED PROTEIN ARC IN CULTURED NEURONS.
|Autores:||Melissa Hott Ogalde (UACH - UNIVERSIDAD AUSTRAL DE CHILE) ; Carolina Martin Bohle (UACH - UNIVERSIDAD AUSTRAL DE CHILE) ; Elizabeth Dimter Lagos (UACH - UNIVERSIDAD AUSTRAL DE CHILE) ; Margarita Concha Grabinger (UACH - UNIVERSIDAD AUSTRAL DE CHILE) ; Carola Otth Lagunas (UACH - UNIVERSIDAD AUSTRAL DE CHILE) |
Herpes Simplex Virus Type 1 (HSV-1) is ubiquitous, neurotropic, and the most common pathogenic cause of sporadic acute encephalitis in humans. Herpes simplex encephalitis is associated with a high mortality rate and significant neurological, neuropsychological, and neurobehavioral sequelae, which afflict patients for life. HSV-1 infects limbic system structures in the central nervous system, and has been suggested as an environmental risk factor for Alzheimer’s disease.
The activity-regulated cytoskeleton-associated protein (Arc) is an immediate early expression protein that has emerged as a key regulator of synaptic plasticity and memory consolidation. Although, the role of Arc in neurogenesis and stress resistance is clear, no studies have analyzed the effects of neuronal infection on Arc expression and neuronal plasticity modulation. In this study, we showed by semi-quantitative RT-PCR, Western Blot and immunofluorescence microscopy analyses that Arc protein and transcript levels are affected in primary neuronal culture infected with HSV-1. Intriguingly, the results show an increase in Arc transcript early after HSV-1 infection (1 hpi) which is maintained until at least 24 hpi independently of viral replication. In contrast, Arc protein was significantly reduced after 4 hpi, reaching almost negligible levels at 24 hpi. These results show that although HSV-1 infection could trigger the transcription of Arc gene and/or reduce the corresponding mRNA decay, basal levels of Arc protein showed a rapid decline most probably by ubiquitination and proteosomal degradation. These results suggest that reduced levels of Arc protein observed during HSV-1 neuronal infection could result in alteration of the cytoskeleton dynamics and neuronal functionality.
Funding: FONDECYT 11080067 and 1120464.
Palavras-chave: ARC, HERPES SIMPLEX VIRUS TYPE 1, SYNAPTIC PLASTICITY