Nature and duration of growth factor signaling through receptor tyrosine kinases regulates HSV-1 latency in neurons.
Publication/Presentation Date
10-21-2010
Abstract
Herpes simplex virus-1 (HSV-1) establishes life-long latency in peripheral neurons where productive replication is suppressed. While periodic reactivation results in virus production, the molecular basis of neuronal latency remains incompletely understood. Using a primary neuronal culture system of HSV-1 latency and reactivation, we show that continuous signaling through the phosphatidylinositol 3-kinase (PI3-K) pathway triggered by nerve growth factor (NGF)-binding to the TrkA receptor tyrosine kinase (RTK) is instrumental in maintaining latent HSV-1. The PI3-K p110α catalytic subunit, but not the β or δ isoforms, is specifically required to activate 3-phosphoinositide-dependent protein kinase-1 (PDK1) and sustain latency. Disrupting this pathway leads to virus reactivation. EGF and GDNF, two other growth factors capable of activating PI3-K and PDK1 but that differ from NGF in their ability to persistently activate Akt, do not fully support HSV-1 latency. Thus, the nature of RTK signaling is a critical host parameter that regulates the HSV-1 latent-lytic switch.
Volume
8
Issue
4
First Page
320
Last Page
330
ISSN
1934-6069
Published In/Presented At
Camarena, V., Kobayashi, M., Kim, J. Y., Roehm, P., Perez, R., Gardner, J., Wilson, A. C., Mohr, I., & Chao, M. V. (2010). Nature and duration of growth factor signaling through receptor tyrosine kinases regulates HSV-1 latency in neurons. Cell host & microbe, 8(4), 320–330. https://doi.org/10.1016/j.chom.2010.09.007
Disciplines
Medicine and Health Sciences
PubMedID
20951966
Department(s)
Department of Medicine
Document Type
Article