Details

Autor(en) / Beteiligte

• Camarena, Vladimir
• Kobayashi, Mariko
• Kim, Ju Youn
• Roehm, Pamela
• Perez, Rosalia
• Gardner, James
• Wilson, Angus C
• Mohr, Ian
• Chao, Moses V

Titel

Nature and duration of growth factor signaling through receptor tyrosine kinases regulates HSV-1 latency in neurons

Ist Teil von

• Cell host & microbe, 2010-10, Vol.8 (4), p.320-330

Ort / Verlag

United States

Erscheinungsjahr

2010

Link zum Volltext

Quelle

MEDLINE

Beschreibungen/Notizen

• 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.