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Mechanisms of Extracellular Immunomodulation Mediated by Infectious Agents Journal of Immunology Research Mechanisms of Extracellular Immunomodulation Mediated by Infectious Agents Guest Editors: Abel Viejo-Borbolla, Hans-Gerhard Burgert, and Frank A. Schildberg Mechanisms of Extracellular Immunomodulation Mediated by Infectious Agents Journal of Immunology Research Mechanisms of Extracellular Immunomodulation Mediated by Infectious Agents Guest Editors: Abel Viejo-Borbolla, Hans-Gerhard Burgert, and Frank A. Schildberg Copyright © 2017 Hindawi. All rights reserved. This is a special issue published in “Journal of Immunology Research.” All articles are open access articles distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. Editorial Board B. D. Akanmori, Congo Eung-Jun Im, USA Aurelia Rughetti, Italy Stuart Berzins, Australia Hidetoshi Inoko, Japan Takami Sato, USA Kurt Blaser, Switzerland Peirong Jiao, China Senthami R. Selvan, USA Federico Bussolino, Italy Taro Kawai, Japan Naohiro Seo, Japan Nitya G. Chakraborty, USA Hiroshi Kiyono, Japan Ethan M. Shevach, USA Robert B. Clark, USA Shigeo Koido, Japan George B. Stefano, USA Mario Clerici, Italy Herbert K. Lyerly, USA TrinaJ.Stewart,Australia Nathalie Cools, Belgium Mahboobeh Mahdavinia, USA Jacek Tabarkiewicz, Poland Mark J. Dobrzanski, USA Eiji Matsuura, Japan Ban-Hock Toh, Australia Nejat K. Egilmez, USA C. J. M. Melief, Netherlands Joseph F. Urban, USA Eyad Elkord, UK Chikao Morimoto, Japan Xiao-Feng Yang, USA Steven E. Finkelstein, USA Hiroshi Nakajima, Japan Qiang Zhang, USA Luca Gattinoni, USA Paola Nistico, Italy Douglas C. Hooper, USA Luigina Romani, Italy Contents Mechanisms of Extracellular Immunomodulation Mediated by Infectious Agents Abel Viejo-Borbolla, Frank A. Schildberg, and Hans-Gerhard Burgert Volume 2017, Article ID 5107527, 3 pages Technologies for Proteome-Wide Discovery of Extracellular Host-Pathogen Interactions Nadia Martinez-Martin Volume 2017, Article ID 2197615, 18 pages IL-10: A Multifunctional Cytokine in Viral Infections José M. Rojas, Miguel Avia, Verónica Martín, and Noemí Sevilla Volume 2017, Article ID 6104054, 14 pages RNA-Seq Based Transcriptome Analysis of the Type I Interferon Host Response upon Vaccinia Virus Infection of Mouse Cells Bruno Hernáez, Graciela Alonso, Juan Manuel Alonso-Lobo, Alberto Rastrojo, Cornelius Fischer, Sascha Sauer, Begoña Aguado, and Antonio Alcamí Volume 2017, Article ID 5157626, 12 pages The Role of Type III Interferons in Hepatitis C Virus Infection and Therapy Janina Bruening, Bettina Weigel, and Gisa Gerold Volume 2017, Article ID 7232361, 12 pages Novel Chemokine-Based Immunotoxins for Potent and Selective Targeting of Cytomegalovirus Infected Cells Katja Spiess, Mads G. Jeppesen, Mikkel Malmgaard-Clausen, Karen Krzywkowski, Thomas N. Kledal, and Mette M. Rosenkilde Volume 2017, Article ID 4069260, 12 pages Hindawi Journal of Immunology Research Volume 2017, Article ID 5107527, 3 pages https://doi.org/10.1155/2017/5107527 Editorial Mechanisms of Extracellular Immunomodulation Mediated by Infectious Agents 1 2 3 Abel Viejo-Borbolla, Frank A. Schildberg, and Hans-Gerhard Burgert 1Institute of Virology, Hannover Medical School, 30625 Hannover, Germany 2Department of Microbiology and Immunobiology, Harvard Medical School, Boston, MA 02115, USA 3School of Life Sciences, University of Warwick, Coventry CV4 7AL, UK Correspondence should be addressed to Abel Viejo-Borbolla; [email protected] Received 11 April 2017; Accepted 11 April 2017; Published 10 May 2017 Copyright © 2017 Abel Viejo-Borbolla et al. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. Secreted proteins and proteins exposed on the cell surface, and microarrays in various flavors, she discusses several mass referred to here together as extracellular proteins (EPs), spectrometry approaches. She also covers briefly genetic are essential in many biological processes, including devel- screens using cDNA libraries and more extensively the newer opment, homeostasis, inflammation, cancer, and pathogen- RNAi-based methods, CRISPR/Cas9 technology, and genetic host interaction. EPs comprising both host and pathogen screens with haploid cells. A valuable addition for the discov- proteins are determinants of the outcome of infection. ery of microbe-host PPIs appears to be the genomic variation Therefore, it is of paramount importance to discover and in the pathogen and host population exposed to it, revealing further characterize these proteins and their interactions positive selection in several cases. Multiple examples are to better understand the infection process and pathogene- given for successful identification of pathogen receptors or sis and to develop novel therapeutic strategies. pathogen-host interactions with components of the immune In this “special issue,” we assembled a group of reviews system using these newer technologies. She also describes the and original research articles that deal with novel technolo- inherent difficulties when applying current high throughput gies for discovery of EPs involved in pathogen-host interac- technologies to this task due to the biochemical nature of tion, discuss the role of classical innate immune cytokines membrane proteins, causing problems with solubility, correct during viral infection, and devise novel therapeutic strategies folding, and posttranslational modifications. Also, the fast using viral receptors as a target. dissociation rates and low affinity for some of these interac- Despite the abundance and relevance of EPs, the iden- tions require further modifications not present in the natural tification and characterization of interactions with proteins proteins. Considering these issues, it becomes clear that high of infectious agents is rather low when compared with that throughput approaches based on soluble PPIs are an excellent of intracellular proteins. Therefore, identifying and charac- screening platform but results must be confirmed by thor- terizing protein–protein interactions (PPI) between EPs ough specific experiments in relevant cells and/or animals. from the host and infectious agents remain challenging One family of secreted proteins that plays key roles in and important tasks. virus-host interaction is that of cytokines, essential to coordi- The recent development of novel technologies is facilitat- nate the innate and adaptive immune responses. Due to their ing this endeavor considerably. In her review, N. Martinez- function, it is not surprising to find that infectious agents Martin discusses classical and novel approaches to discover have devised many strategies to modulate their activities. PPIs and explains their application to the identification of These strategies include the expression of proteins with the PPI between infectious agents and host proteins. Starting ability to bind cytokines and/or modulate their interaction from biochemical and biophysical approaches, such as SPR with the cytokine receptor, as well as the expression of 2 Journal of Immunology Research transmembrane receptor and cytokine homologs. Among the response to HCV focusing on in vitro and in vivo studies cytokines, the interferons (IFN) are essential in protecting addressing HCV-IFN-λ interaction. The authors discuss the cells from viruses through the induction of an antiviral status. interesting and initially counterintuitive data indicating that There are three types of IFN discovered to date: the multigene high levels of IFN-λ correlate with HCV chronicity of infec- cytokine family of type I IFN containing IFN-α and β as pro- tion. Also, they explain the relationship between IFN-λ poly- totypes, type II IFN including only IFN-γ, and type III IFN morphism, HCV spontaneous clearance, and the response to containing IFN-λ1–4. Two manuscripts deal with the interac- anti-HCV treatment. tion between IFN and virus infection in this special issue. The review article by J. M. Rojas et al. focuses on the anti- In the original research manuscript contributed by B. inflammatory master regulator IL-10 and its implications Hernáez et al., the authors study the effect of vaccinia during viral infections. The main function of IL-10 is to limit virus (VACV) and its secreted, IFN-binding protein, B18, immunopathology during inflammation, thereby protecting on the cellular type I IFN response. VACV is a member the host from tissue damage and loss of organ function. IL- of the Poxviridae, large double stranded DNA viruses that 10 is not only expressed by a variety of immune cells but is also encode many immunomodulatory proteins. In particular, able to regulate the activity of immune cells. It is, therefore, they express secreted proteins with the ability to bind type not surprising that viruses exploit this central immune regula- I–III IFN [1–3]. VACV is one of the best-studied poxviruses tory pathway to evade immunity, leading to chronic/latent in part due to its use as the vaccine employed during the infections, and that detailed knowledge of the IL-10 effects is world health organization-led campaign to eradicate small- of high relevance. In this review, J. M. Rojas et al. discuss pox, caused by the deadly variola virus. VACV expresses sev- how the spatial and temporal delivery of IL-10 influences eral genes whose protein products interfere with the IFN the course of viral infections. The focus
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