Identification of an important immunological difference between virulent varicella-zoster virus and its avirulent vaccine

• Verfasst von: Gutzeit, Cindy [VerfasserIn]
• Verfasst von: Raftery, Martin J. [VerfasserIn]
• Verfasst von: Peiser, Matthias [VerfasserIn]
• Verfasst von: Tischer, Karsten B. [VerfasserIn]
• Verfasst von: Ulrich, Martina [VerfasserIn]
• Verfasst von: Eberhardt, Melanie [VerfasserIn]
• Verfasst von: Stockfleth, Eggert [VerfasserIn]
• Verfasst von: Giese, Thomas [VerfasserIn]
• Verfasst von: Sauerbrei, Andreas [VerfasserIn]
• Verfasst von: Morita, Craig T. [VerfasserIn]
• Verfasst von: Schönrich, Günther [VerfasserIn]
• Titel: Identification of an important immunological difference between virulent varicella-zoster virus and its avirulent vaccine
• Titelzusatz: viral disruption of dendritic cell instruction
• Verf.angabe: Cindy Gutzeit, Martin J. Raftery, Matthias Peiser, Karsten B. Tischer, Martina Ulrich, Melanie Eberhardt, Eggert Stockfleth, Thomas Giese, Andreas Sauerbrei, Craig T. Morita, and Günther Schönrich
• E-Jahr: 2010
• Jahr: 2010 Jul 1
• Umfang: 22 S.
• Fussnoten: Gesehen am 05.06.2023
• Titel Quelle: Enthalten in: The journal of immunology
• Ort Quelle: Bethesda, Md. : Soc., 1916
• Jahr Quelle: 2010
• Band/Heft Quelle: 185(2010), 1, Seite 488-497
• ISSN Quelle: 1550-6606
• DOI: doi:10.4049/jimmunol.0902817
• Datenträger: Online-Ressource
• Sprache: eng
• Sach-SW: Cells, Cultured
• Sach-SW: Chickenpox Vaccine
• Sach-SW: Coculture Techniques
• Sach-SW: Dendritic Cells
• Sach-SW: Herpes Zoster
• Sach-SW: Herpesvirus 3, Human
• Sach-SW: Herpesvirus Vaccines
• Sach-SW: Humans
• Sach-SW: Immune Evasion
• Sach-SW: Interleukin-12
• Sach-SW: Middle Aged
• Sach-SW: Monocytes
• Sach-SW: Signal Transduction
• Sach-SW: Th1 Cells
• Sach-SW: Vaccines, Attenuated
• Sach-SW: Virulence
• K10plus-PPN: 1847419526

Abstract

Virulent varicella-zoster virus (VZV) can spread in immunocompetent humans, resulting in symptoms mostly of the skin. In contrast, vaccine Oka (V-Oka), the attenuated VZV vaccine strain, only rarely causes clinical reactions. The mechanisms underlying these pathogenetic differences are unclear. In this study, we comparatively analyzed the ability of virulent VZV and V-Oka to modulate instruction of dendritic cells (DCs) by innate signals. DCs isolated from normal human skin were susceptible to infection with VZV and V-Oka. Moreover, inflammatory DCs, which play a crucial role in the stimulation of Th1 immune responses, accumulated in herpes zoster lesions. Infection of inflammatory DCs generated in vitro with virulent VZV or V-Oka resulted in upregulation of CD1c. Upon coculture with CD1c-restricted innate cells, DCs developed a mature phenotype whether infected with virulent VZV or V-Oka. Intriguingly, a striking difference was detected on the functional level. The release of IFN-gamma and IL-12, the signature cytokines of Th1 responses, was enhanced by V-Oka but blocked by virulent VZV. V-Oka and virulent VZV efficiently synergized with CD40L, eliminating the possibility that CD40 signaling was a target of VZV-associated immune evasion. Instead, virulent VZV selectively interfered with signaling through TLR2, which is known to sense VZV. Thus, virulent VZV subverts Th1-promoting instruction of human DCs by blocking TLR2-mediated innate signals that prime IL-12 production by DCs. Taken together, our results demonstrate a novel immune-evasion mechanism of virulent VZV that has been lost during the attenuation process leading to the VZV vaccine strain.