Conserved Fever Pathways across Vertebrates: A Herpesvirus Expressed Decoy TNF-α Receptor Delays Behavioral Fever in Fish.
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.
Immunology-Vaccinology, FARAH, Faculty of Veterinary Medicine, University of Liège, Liège 4000, Belgium; Department of Evolutionary Immunology, Institute of Zoology, Jagiellonian University, Krakow 30-387, Poland.
Krzysztof
K
Rakus
Immunology-Vaccinology, FARAH, Faculty of Veterinary Medicine, University of Liège, Liège 4000, Belgium.
Maygane
M
Ronsmans
Cell Biology and Immunology Group, Department of Animal Sciences, Wageningen University and Research, Wageningen 6708WD, the Netherlands.
Maria
M
Forlenza
Immunology-Vaccinology, FARAH, Faculty of Veterinary Medicine, University of Liège, Liège 4000, Belgium.
Maxime
M
Boutier
Cell Biology and Immunology Group, Department of Animal Sciences, Wageningen University and Research, Wageningen 6708WD, the Netherlands.
M Carla
MC
Piazzon
Immunology-Vaccinology, FARAH, Faculty of Veterinary Medicine, University of Liège, Liège 4000, Belgium; Maria Sklodowska-Curie Memorial Cancer Center and Institute of Oncology, Gliwice 44-101, Poland.
Joanna
J
Jazowiecka-Rakus
Division of Biomedical and Life Sciences, Faculty of Health and Medicine, Lancaster University, Lancaster LA1 4YW, UK.
Derek
D
Gatherer
Instituto Gulbenkian de Ciência, Oeiras 2781-156, Portugal.
Alekos
A
Athanasiadis
Biostatistics and Bioinformatics, FARAH, University of Liège, Liège 4000, Belgium.
Frédéric
F
Farnir
MRC - University of Glasgow Centre for Virus Research, Glasgow G61 1QH, UK.
Andrew J
AJ
Davison
Virologie et Immunologie Moléculaires, INRA, Jouy-en-Josas 78352, France.
Pierre
P
Boudinot
de Duve Institute, Université Catholique de Louvain, Brussels 1200, Belgium.
Thomas
T
Michiels
Cell Biology and Immunology Group, Department of Animal Sciences, Wageningen University and Research, Wageningen 6708WD, the Netherlands.
Geert F
GF
Wiegertjes
Immunology-Vaccinology, FARAH, Faculty of Veterinary Medicine, University of Liège, Liège 4000, Belgium. Electronic address: a.vdplasschen@ulg.ac.be.
Alain
A
Vanderplasschen
D000818:Animals; D001833:Body Temperature Regulation; D002347:Carps / Q000821:virology*; D017353:Gene Deletion; D015967:Gene Expression Regulation, Viral; D006564:Herpesviridae / Q000235:genetics / Q000502:physiology*; D006566:Herpesviridae Infections / Q000662:veterinary*; D054884:Host-Pathogen Interactions / Q000235:genetics; D018124:Receptors, Tumor Necrosis Factor / Q000235:genetics / Q000378:metabolism*; D013696:Temperature; D014764:Viral Proteins / Q000235:genetics / Q000378:metabolism*; D014779:Virus Replication
D018124:Receptors, Tumor Necrosis Factor; D014764:Viral Proteins
behavioral fever; cyprinid herpesvirus 3; fever; herpesvirus; host-virus interactions; immune evasion mechanisms; innate immunity; pathogen-host-environment interplay; tumor necrosis factor α; viral decoy receptor for cytokine