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Herpesvirus quiescence in neuronal cells IV: Virus activation induced by pituitary adenylate cyclase-activating polypeptide (PACAP) involves the protein kinase A pathway

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Abstract

Pituitary adenylate cyclase-activating polypeptide (PACAP) is a naturally occurring peptide found in the central nervous system that plays a role in somatosensory processing and activation of protein kinase A (PKA) and protein kinase C (PKC). Because activation of PKA or PKC results in reactivation of HSV-1 from latently infected embryonic neuronal cells, PACAP was used to evaluate HSV-1 activation from quiescently infected (QIF)-PC12 cells. Our studies demonstrate that physiologically relevant concentrations of PACAP38 and PACAP27 induce HSV-1 activation from QIF-PC12 cell cultures in a dose-dependent fashion. PACAP-induced activation of virus was significantly impaired by the PKA-inhibitor, H-89 (20 μM), whereas treatment with the PKC-inhibitor, GF109203X (1 μM), was without affect. Additionally, direct activation of PKA with cAMP analogs, 8-(4-chlorophenylthio)- and dibutyryl-cAMP, only partially mimicked the effect of PACAP on virus activation. Taken together, PACAP induced HSV-1 activation from QIF-PC12 cells involves the PKA and possibly cAMP-independent pathways. This report is the first to demonstrate that PACAP induces HSV-1 activation from a quiescent state and that this in vitro cell model is useful for studying early inductive events that lead to virus production from quiescence.

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Authors and Affiliations

  1. Oral Medicine Section MN 118, Department of Oral Health Practice, University of Kentucky College of Dentistry, 800 Rose Street, 40536-0297, Lexington, KY, USA

    Robert J. Danaher, Amber D. Savells-Arb, Samuel A. Black, Robert J. Jacob & Craig S. Miller

  2. Department of Microbiology and Immunology, Markey Cancer Center, University of Kentucky College of Dentistry and College of Medicine, Lexington, Kentucky, USA

    Robert J. Danaher, Amber D. Savells-Arb, Robert J. Jacob & Craig S. Miller

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  1. Robert J. Danaher
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  2. Amber D. Savells-Arb
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  3. Samuel A. Black
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  4. Robert J. Jacob
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  5. Craig S. Miller
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Correspondence to Craig S. Miller.

Additional information

Fourth in the series. III was published as “Herpesvirus quiescence in neuronal cells: Antiviral conditions not required to establish and maintain HSV-2 quiescence” in Journal of NeuroVirology, volume 6, issue 4, pages 296–302.

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Danaher, R.J., Savells-Arb, A.D., Black, S.A. et al. Herpesvirus quiescence in neuronal cells IV: Virus activation induced by pituitary adenylate cyclase-activating polypeptide (PACAP) involves the protein kinase A pathway. Journal of NeuroVirology 7, 163–168 (2001). https://doi.org/10.1080/13550280152058825

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  • DOI: https://doi.org/10.1080/13550280152058825

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