Conserved Fever Pathways across Vertebrates: A Herpesvirus Expressed Decoy TNF-α Receptor Delays Behavioral Fever in Fish

Publication date: 8 February 2017
Source:Cell Host & Microbe, Volume 21, Issue 2
Author(s): Krzysztof Rakus, Maygane Ronsmans, Maria Forlenza, Maxime Boutier, M. Carla Piazzon, Joanna Jazowiecka-Rakus, Derek Gatherer, Alekos Athanasiadis, Frédéric Farnir, Andrew J. Davison, Pierre Boudinot, Thomas Michiels, Geert F. Wiegertjes, Alain Vanderplasschen
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

Teaser

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.


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