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Genes & Dev. 26 (14): 1527-1532

Copyright © 2012 by Cold Spring Harbor Laboratory Press.


RESEARCH COMMUNICATION

Control of viral latency in neurons by axonal mTOR signaling and the 4E-BP translation repressor

Mariko Kobayashi1, Angus C. Wilson1,2, Moses V. Chao3,4,5,6,7,, and Ian Mohr1,2,8

1 Department of Microbiology,
2 New York University Cancer Institute,
3 Molecular Neurobiology Program, Skirball Institute for Biomolecular Medicine,
4 Department of Cell Biology,
5 Department of Physiology and Neuroscience,
6 Department of Psychiatry,
7 Center for Neural Science, New York University School of Medicine, New York, New York 10016, USA

Abstract: Latent herpes simplex virus-1 (HSV1) genomes in peripheral nerve ganglia periodically reactivate, initiating a gene expression program required for productive replication. Whether molecular cues detected by axons can be relayed to cell bodies and harnessed to regulate latent genome expression in neuronal nuclei is unknown. Using a neuron culture model, we found that inhibiting mTOR, depleting its regulatory subunit raptor, or inducing hypoxia all trigger reactivation. While persistent mTORC1 activation suppressed reactivation, a mutant 4E-BP (eIF4E-binding protein) translational repressor unresponsive to mTORC1 stimulated reactivation. Finally, inhibiting mTOR in axons induced reactivation. Thus, local changes in axonal mTOR signaling that control translation regulate latent HSV1 genomes in a spatially segregated compartment.

Key Words: eIF4E-binding protein 4E-BP1 • local translational control • mTOR signaling • neurons • virus latency

Received for publication March 1, 2012. Accepted for publication June 6, 2012.


8 Corresponding author

Email ian.mohr{at}med.nyu.edu

Supplemental material is available for this article.

Article is online at http://www.genesdev.org/cgi/doi/10.1101/gad.190157.112.


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