Abstract
Varicella zoster virus (VZV), a human neurotropic alphaherpesvirus, becomes latent after primary infection and reactivates to produce zoster. To study VZV latency and reactivation, human trigeminal ganglia removed within 24 h after death were mechanically dissociated, randomly distributed into six-well tissue culture plates and incubated with reagents to inactivate nerve growth factor (NGF) or phosphoinositide 3-kinase (PI3-kinase) pathways. At 5 days, VZV DNA increased in control and PI3-kinase inhibitor-treated cultures to the same extent, but was significantly more abundant in anti-NGF-treated cultures (p = 0.001). Overall, VZV DNA replication is regulated in part by an NGF pathway that is PI3-kinase-independent.
Keywords:
Human; Latency; Nerve growth factor; Phosphoinositide-3-kinase; Trigeminal ganglion; VZV.
MeSH terms
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Adult
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Aged
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Antibodies, Neutralizing / pharmacology
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Autopsy
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DNA Replication*
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DNA, Viral / biosynthesis
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DNA, Viral / genetics*
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Gene Expression Regulation
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Herpes Zoster / genetics
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Herpes Zoster / metabolism
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Herpes Zoster / pathology
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Herpes Zoster / virology
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Herpesvirus 3, Human / genetics*
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Herpesvirus 3, Human / metabolism
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Herpesvirus 3, Human / pathogenicity
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Host-Pathogen Interactions
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Humans
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Male
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Middle Aged
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Nerve Growth Factor / antagonists & inhibitors
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Nerve Growth Factor / genetics*
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Nerve Growth Factor / metabolism
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Phosphatidylinositol 3-Kinases / genetics*
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Phosphatidylinositol 3-Kinases / metabolism
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Phosphoinositide-3 Kinase Inhibitors
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Protein Kinase Inhibitors / pharmacology
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Signal Transduction
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Tissue Culture Techniques
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Trigeminal Ganglion / drug effects
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Trigeminal Ganglion / virology
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Virus Activation*
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Virus Latency
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Virus Replication*
Substances
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Antibodies, Neutralizing
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DNA, Viral
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Phosphoinositide-3 Kinase Inhibitors
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Protein Kinase Inhibitors
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Nerve Growth Factor