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Zhangfei, a novel regulator of the human nerve growth factor receptor, trkA

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Abstract

The replication of herpes simplex virus (HSV) in epithelial cells, and during reactivation from latency in sensory neurons, depends on a ubiquitous cellular protein called host cell factor (HCF). The HSV transactivator, VP16, which initiates the viral replicative cycle, binds HCF as do some other cellular proteins. Of these, the neuronal transcription factor Zhangfei suppresses the ability of VP16 to initiate the replicative cycle. It also suppresses Luman, another cellular transcription factor that binds HCF. Interactions of nerve growth factor (NGF) and its receptor tropomyosin-related kinase (trkA) appear to be critical for maintaining HSV latency. Because the neuronal transcription factor Brn3a, which regulates trkA expression, has a motif for binding HCF, we investigated if Zhangfei had an effect on its activity. We found that Brn3a required HCF for activating the trkA promoter and Zhangfei suppressed its activity in non-neuronal cells. However, in neuron-like NGF-differentiated PC12 cells, both Brn3a and Zhangfei activated the trkA promoter and induced the expression of endogenous trkA. In addition, capsaicin, a stressor, which activates HSV in in vitro models of latency, decreased levels of Zhangfei and trkA transcripts in NGF-differentiated PC12 cells.

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  1. Ximena Valderrama

    Present address: Instituto de Produccioín Animal, Facultad de Ciencias Agrarias, Universidad Austral de Chile, Valdivia, Chile

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  1. Department of Veterinary Microbiology, Western College of Veterinary Medicine, University of Saskatchewan, 52 Campus Road, S7N5B4, Saskatoon, Saskatchewan, Canada

    Ximena Valderrama, Noreen Rapin & Vikram Misra

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  1. Ximena Valderrama
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  2. Noreen Rapin
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  3. Vikram Misra
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Correspondence to Vikram Misra.

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This work was supported by a Discovery Grant to V.M. from the Natural Sciences and Engineering Research Council of Canada. X.V. was supported partially by the Discovery grant and partially by a University of Saskatchewan graduate scholarship.

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Valderrama, X., Rapin, N. & Misra, V. Zhangfei, a novel regulator of the human nerve growth factor receptor, trkA. Journal of NeuroVirology 14, 425–436 (2008). https://doi.org/10.1080/13550280802275904

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