Alekos Athanasiadis, Maxime Boutier, Maygane Ronsmans, Thomas Michiels, Krzysztof Rakus, Andrew J. Davison, Derek Gatherer, M. Carla Piazzon, Joanna Jazowiecka-Rakus, Alain Vanderplasschen, Geert F. Wiegertjes, Frédéric Farnir, Maria Forlenza, Pierre Boudinot, Immunology-Vaccinology, FARAH, Faculty of Veterinary Medicine, Université de Liège, Department of Evolutionary Immunology, Institute of Zoology, Jagiellonian University, Cell Biology and Immunology Group, Department of Animal Sciences, Wageningen University and Research Center (WUR), Institute of Oncology, Maria Skłodowska Curie Memorial Cancer Center, Immunology-Vaccinology, FARAH, Division of Biomedical and Life Sciences, Faculty of Health and Medicine, Lancaster University, Instituto Gulbenkian de Ciência, Unité de recherche Virologie et Immunologie Moléculaires (VIM), Institut National de la Recherche Agronomique (INRA), Université Catholique de Louvain, University of Liege, Belgian Science Policy [BELVIR IAP7/45], Fonds National Belge de la Recherche Scientifique [T.0153.13, 1.5.176.12], FCT [IF/00641/2013], European Community [PIEF-GA-2011-302444 FISHIL10], Netherlands Organization for Scientific Research (NWO) under Veni [11200], UK Medical Research Council [MC_UU_12014/3], Wageningen University and Research [Wageningen] (WUR), Unité de recherche Virologie et Immunologie Moléculaires (VIM (UR 0892)), and Université Catholique de Louvain = Catholic University of Louvain (UCL)
Summary Both endotherms and ectotherms (e.g., fish) increase their body temperature to limit pathogen infection. Ectotherms do so by moving to warmer places, hence the term “behavioral fever.” We studied the manifestation of behavioral fever in the common carp infected by cyprinid herpesvirus 3, a native carp pathogen. Carp maintained at 24°C died from the infection, whereas those housed in multi-chamber tanks encompassing a 24°C–32°C gradient migrated transiently to the warmest compartment and survived as a consequence. Behavioral fever manifested only at advanced stages of infection. Consistent with this, expression of CyHV-3 ORF12, encoding a soluble decoy receptor for TNF-α, delayed the manifestation of behavioral fever and promoted CyHV-3 replication in the context of a temperature gradient. Injection of anti-TNF-α neutralizing antibodies suppressed behavioral fever, and decreased fish survival in response to infection. This study provides a unique example of how viruses have evolved to alter host behavior to increase fitness., Graphical Abstract, Highlights • Behavioral fever exhibited by carp in response to CyHV-3 infection is host beneficial • CyHV-3 ORF12 delays behavioral fever expression, thereby promoting its own replication • CyHV-3 ORF12 encodes a soluble decoy receptor for TNF-α • TNF-α is a mediator of behavioral fever expressed by CyHV-3 infected carp, Ectotherms can express behavioral fever to limit pathogen infection. Rakus et al. show that a carp herpesvirus delays behavioral fever by expressing a soluble decoy receptor for TNF-α, thus promoting its own replication. In addition, they demonstrate a role for TNF-α in the induction of behavioral fever in teleost fish.