Systems analysis reveals complex biological processes during virus infection fate decisions

  1. Andreas Meyerhans1,11
  1. 1Infection Biology Laboratory, Department of Experimental and Health Sciences (DCEXS), Universitat Pompeu Fabra, Barcelona, Catalonia 08003, Spain;
  2. 2CNAG-CRG, Center for Genomic Regulation (CRG), Barcelona Institute of Science and Technology, 08028 Barcelona, Spain;
  3. 3Universitat Pompeu Fabra (UPF), Barcelona, Catalonia 08003, Spain;
  4. 4IRTA, Centre de Recerca en Sanitat Animal (CReSA-IRTA-UAB), Campus de la Universitat Autònoma de Barcelona, 08193 Bellaterra, Barcelona, Catalonia, Spain;
  5. 5Laboratory of Proteomics and Protein Chemistry, DCEXS, Universitat Pompeu Fabra, 08003 Barcelona, Spain;
  6. 6Department of Immunology, Institute of Advanced Medicine, Wakayama Medical University, Wakayama 641-8509, Japan;
  7. 7Laboratory for Immune Regulation, World Premier International Research Center Initiative, Immunology Frontier Research Center, Osaka University, Osaka 565-0871, Japan;
  8. 8Marchuk Institute of Numerical Mathematics, Russian Academy of Sciences, Moscow, 119333, Russia;
  9. 9Sechenov First Moscow State Medical University, Moscow, 119991, Russia;
  10. 10Institute for Immunobiology, Kantonsspital St. Gallen, 9007 St. Gallen, Switzerland;
  11. 11Institució Catalana de Recerca i Estudis Avançats (ICREA), Barcelona, 08003, Spain

  1. ↵12 These authors contributed equally to this work.

  • ↵13 Present address: Department of Immunology, Weizmann Institute of Science, Rehovot, 76100, Israel

  • Corresponding author: andreas.meyerhans{at}upf.edu

    • Abstract

    The processes and mechanisms of virus infection fate decisions that are the result of a dynamic virus-immune system interaction with either an efficient effector response and virus elimination or an alleviated immune response and chronic infection are poorly understood. Here, we characterized the host response to acute and chronic lymphocytic choriomeningitis virus (LCMV) infections by gene coexpression network analysis of time-resolved splenic transcriptomes. First, we found an early attenuation of inflammatory monocyte/macrophage prior to the onset of T cell exhaustion, and second, a critical role of the XCL1-XCR1 communication axis during the functional adaptation of the T cell response to the chronic infection state. These findings not only reveal an important feedback mechanism that couples T cell exhaustion with the maintenance of a lower level of effector T cell response but also suggest therapy options to better control virus levels during the chronic infection phase.

    Footnotes

    • Received July 3, 2018.
    • Accepted May 14, 2019.

    This article is distributed exclusively by Cold Spring Harbor Laboratory Press for the first six months after the full-issue publication date (see http://genome.cshlp.org/site/misc/terms.xhtml). After six months, it is available under a Creative Commons License (Attribution-NonCommercial 4.0 International), as described at http://creativecommons.org/licenses/by-nc/4.0/.

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    This Article

    1. Published in Advance May 28, 2019, doi: 10.1101/gr.241372.118 Genome Res. 29: 907-919 © 2019 Argilaguet et al.; Published by Cold Spring Harbor Laboratory Press

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    1. Profile for Meyerhans, A.http://orcid.org/0000-0003-0620-5317

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