Department of Biomedicine, Aarhus University, Aarhus, Denmark; Center for Immunology of Viral Infections, Aarhus University, Aarhus, Denmark; Department of Rheumatology and Inflammation Research, Institute of Medicine, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden; Corresponding author
Thomas Pradeu
CNRS UMR 5164 ImmunoConcept, University of Bordeaux, Bordeaux, France; Department of Biological and Medical Sciences, University of Bordeaux, Bordeaux, France; Chapman University, Orange, CA, USA
Andreas Pichlmair
Center for Immunology of Viral Infections, Aarhus University, Aarhus, Denmark; Technical University of Munich, School of Medicine, Institute of Virology, Munich, Germany; German Center for Infection Research (DZIF), Partner Site Munich, Munich, Germany
K. Brad Wray
Center for Immunology of Viral Infections, Aarhus University, Aarhus, Denmark; Centre for Science Studies, Aarhus University, Aarhus, Denmark; Aarhus Institute of Advanced Studies, Aarhus University, Aarhus, Denmark
Jacob Giehm Mikkelsen
Department of Biomedicine, Aarhus University, Aarhus, Denmark; Center for Immunology of Viral Infections, Aarhus University, Aarhus, Denmark
David Olagnier
Department of Biomedicine, Aarhus University, Aarhus, Denmark; Center for Immunology of Viral Infections, Aarhus University, Aarhus, Denmark
Trine H. Mogensen
Department of Biomedicine, Aarhus University, Aarhus, Denmark; Center for Immunology of Viral Infections, Aarhus University, Aarhus, Denmark; Department of Infectious Diseases, Aarhus University Hospital, Aarhus, Denmark
Summary: Early host defense eliminates many viruses before infections are established while clearing others so they remain subclinical or cause only mild disease. The field of immunology has been shaped by broad concepts, including the pattern recognition theory that currently dominates innate immunology. Focusing on early host responses to virus infections, we analyze the literature to build a working hypothesis for the principles that govern the early line of cellular antiviral defense. Aiming to ultimately arrive at a criteria-based theory with strong explanatory power, we propose that both controlling infection and limiting inflammation are key drivers for the early cellular antiviral response. This response, which we suggest is exerted by a set of “microbe- and inflammation-restricting mechanisms,” directly restrict viral replication while also counteracting inflammation. Exploring the mechanisms and physiological importance of the early layer of cellular antiviral defense may open further lines of research in immunology.
