Article ; Online: CD40 ligand exhibits a direct antiviral effect on Herpes Simplex Virus type-1 infection via a PI3K-dependent, autophagy-independent mechanism.
2015 Volume 27, Issue 6, Page(s) 1253–1263
Abstract: The interaction between CD40 and its ligand, CD40L/CD154, is crucial for the efficient initiation and regulation of immune responses against viruses. Herpes Simplex Virus type-1 (HSV-1) is a neurotropic virus capable of manipulating host responses and ... ...
| Abstract | The interaction between CD40 and its ligand, CD40L/CD154, is crucial for the efficient initiation and regulation of immune responses against viruses. Herpes Simplex Virus type-1 (HSV-1) is a neurotropic virus capable of manipulating host responses and exploiting host proteins to establish productive infection. Herein we have examined the impact of CD40L-mediated CD40 activation on HSV-1 replication in U2OS cells stably expressing the CD40 receptor. Treatment of these cells with CD40L significantly reduced the HSV-1 progeny virus compared to non-treated cells. The activation of CD40 signaling did not affect the binding of HSV-1 virions on the cell surface but rather delayed the translocation of VP16 to the nucleus, affecting all stages of viral life cycle. Using pharmacological inhibitors and RNAi we show that inhibition of PI3 kinase but not autophagy reverses the effects of CD40L on HSV-1 replication. Collectively, these data demonstrate that CD40 activation exerts a direct inhibitory effect on HSV-1, initiating from the very early stages of the infection by exploiting PI3 kinase-dependent but autophagy-independent mechanisms. |
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| MeSH term(s) | Anthracenes/pharmacology ; Antiviral Agents/pharmacology ; Autophagy/drug effects ; Autophagy-Related Protein 5 ; Benzylamines/pharmacology ; CD40 Ligand/genetics ; CD40 Ligand/metabolism ; Cell Line, Tumor ; Cell Nucleus/metabolism ; Chromones/pharmacology ; Herpes Simplex Virus Protein Vmw65/metabolism ; Herpesvirus 1, Human/drug effects ; Herpesvirus 1, Human/physiology ; Humans ; JNK Mitogen-Activated Protein Kinases/antagonists & inhibitors ; JNK Mitogen-Activated Protein Kinases/metabolism ; Macrolides/pharmacology ; Microtubule-Associated Proteins/antagonists & inhibitors ; Microtubule-Associated Proteins/genetics ; Microtubule-Associated Proteins/metabolism ; Morpholines/pharmacology ; Phosphatidylinositol 3-Kinases/metabolism ; Phosphoinositide-3 Kinase Inhibitors ; Quinazolines/pharmacology ; RNA Interference ; RNA, Small Interfering/metabolism ; Signal Transduction/drug effects ; Virus Replication/drug effects |
| Chemical Substances | ATG5 protein, human ; Anthracenes ; Antiviral Agents ; Autophagy-Related Protein 5 ; Benzylamines ; Chromones ; Herpes Simplex Virus Protein Vmw65 ; MAP1LC3A protein, human ; Macrolides ; Microtubule-Associated Proteins ; Morpholines ; Phosphoinositide-3 Kinase Inhibitors ; Quinazolines ; RNA, Small Interfering ; spautin-1 ; CD40 Ligand (147205-72-9) ; pyrazolanthrone (1TW30Y2766) ; 2-(4-morpholinyl)-8-phenyl-4H-1-benzopyran-4-one (31M2U1DVID) ; bafilomycin A1 (88899-55-2) ; JNK Mitogen-Activated Protein Kinases (EC 2.7.11.24) |
| Language | English |
| Publishing date | 2015-03-10 |
| Publishing country | England |
| Document type | Journal Article ; Research Support, Non-U.S. Gov't |
| ZDB-ID | 1002702-6 |
| ISSN | 1873-3913 ; 0898-6568 |
| ISSN (online) | 1873-3913 |
| ISSN | 0898-6568 |
| DOI | 10.1016/j.cellsig.2015.03.002 |
| Database | MEDical Literature Analysis and Retrieval System OnLINE |
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