Regulation of NKG2D and DNAM-1 ligand expression in HCMV infected fibroblasts: role of the DNA damage response pathway and of viral replication.

Abstract

Event Abstract Back to Event Regulation of NKG2D and DNAM-1 ligand expression in HCMV infected fibroblasts: role of the DNA damage response pathway and of viral replication. Benedetta Pignoloni1*, Valentina Dell'Oste2, Giorgio Gribaudo3, Marco Cippitelli1, Cinzia Fionda1, Giulia Malgarini1, Alessandra Zingoni1, Santo Landolfo2, Angela Santoni1 and Cristina Cerboni1* 1 Sapienza, University of Rome, Department of Molecular Medicine, Italy 2 University of Turin, Department of Public Health and Microbiology, Italy 3 University of Turin, Department of Life Sciences and Systems Biology, Italy Human cytomegalovirus (HCMV) evolved several strategies to evade NK and cytotoxic T cells, including the specific down-modulation of ligands of the activating receptors NKG2D and DNAM-1. Despite this, we believe that there is a window of opportunity to develop an adequate immune response, during which activating molecules can be expressed as a consequence of viral-induced stress response, and before immune-evasion events occurs. To this purpose we focused on MICA, ULBP3 (NKG2DL) and PVR (DNAM-1L) expression, and investigated the role of the DNA damage response (DDR) and its central mediator ATM, that is crucial in the regulation of NKG2DL and DNAM-1L expression. Human primary fibroblasts (HFF) infected with the AD169 strain significantly increased MICA, ULBP3 and PVR expression. However, if infected cells were treated with caffeine, an inhibitor of ATM/ATR kinases, ligand up-regulation was prevented, demonstrating that the DDR pathway was crucial in regulating these activating molecules also in the context of HCMV infection. Notably, DDR was necessary for HCMV productive replication as well, since little or no infectious virus was recovered from caffeine-treated cells. Ligand up-regulation was however observed to be HCMV replication-independent, as demonstrated by using Foscarnet, an inhibitor of viral DNA elongation, and related to HCMV-mediated exit from G0/G1 phases of the cell cycle. We are currently addressing the involvement of early viral proteins in ligand up-regulation capable of modulating early events responsible for an effective immune response. Keywords: NK cells, Human Cytomegalovirus, NKG2D, DNAM-1, DDR Conference: 15th International Congress of Immunology (ICI), Milan, Italy, 22 Aug - 27 Aug, 2013. Presentation Type: Abstract Topic: Innate immunity Citation: Pignoloni B, Dell'Oste V, Gribaudo G, Cippitelli M, Fionda C, Malgarini G, Zingoni A, Landolfo S, Santoni A and Cerboni C (2013). Regulation of NKG2D and DNAM-1 ligand expression in HCMV infected fibroblasts: role of the DNA damage response pathway and of viral replication.. Front. Immunol. Conference Abstract: 15th International Congress of Immunology (ICI). doi: 10.3389/conf.fimmu.2013.02.00253 Copyright: The abstracts in this collection have not been subject to any Frontiers peer review or checks, and are not endorsed by Frontiers. They are made available through the Frontiers publishing platform as a service to conference organizers and presenters. The copyright in the individual abstracts is owned by the author of each abstract or his/her employer unless otherwise stated. Each abstract, as well as the collection of abstracts, are published under a Creative Commons CC-BY 4.0 (attribution) licence (https://creativecommons.org/licenses/by/4.0/) and may thus be reproduced, translated, adapted and be the subject of derivative works provided the authors and Frontiers are attributed. For Frontiers’ terms and conditions please see https://www.frontiersin.org/legal/terms-and-conditions. Received: 13 Mar 2013; Published Online: 22 Aug 2013. * Correspondence: Dr. Benedetta Pignoloni, Sapienza, University of Rome, Department of Molecular Medicine, Rome, 00161, Italy, benedetta.pignoloni@uniroma1.it Prof. Cristina Cerboni, Sapienza, University of Rome, Department of Molecular Medicine, Rome, 00161, Italy, cristina.cerboni@uniroma1.it Login Required This action requires you to be registered with Frontiers and logged in. To register or login click here. Abstract Info Abstract The Authors in Frontiers Benedetta Pignoloni Valentina Dell'Oste Giorgio Gribaudo Marco Cippitelli Cinzia Fionda Giulia Malgarini Alessandra Zingoni Santo Landolfo Angela Santoni Cristina Cerboni Google Benedetta Pignoloni Valentina Dell'Oste Giorgio Gribaudo Marco Cippitelli Cinzia Fionda Giulia Malgarini Alessandra Zingoni Santo Landolfo Angela Santoni Cristina Cerboni Google Scholar Benedetta Pignoloni Valentina Dell'Oste Giorgio Gribaudo Marco Cippitelli Cinzia Fionda Giulia Malgarini Alessandra Zingoni Santo Landolfo Angela Santoni Cristina Cerboni PubMed Benedetta Pignoloni Valentina Dell'Oste Giorgio Gribaudo Marco Cippitelli Cinzia Fionda Giulia Malgarini Alessandra Zingoni Santo Landolfo Angela Santoni Cristina Cerboni Related Article in Frontiers Google Scholar PubMed Abstract Close Back to top Javascript is disabled. Please enable Javascript in your browser settings in order to see all the content on this page.