Attenuation of the influenza virus sickness behavior in mice deficient in Toll-like receptor 3

Jeannine A Majde; Levente Kapás; Stewart G Bohnet; Alok De; James M Krueger

doi:10.1016/j.bbi.2009.10.011

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Attenuation of the influenza virus sickness behavior in mice deficient in Toll-like receptor 3

Journal article

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Attenuation of the influenza virus sickness behavior in mice deficient in Toll-like receptor 3

Jeannine A Majde, Levente Kapás, Stewart G Bohnet, Alok De and James M Krueger

Brain, behavior, and immunity, Vol.24(2), pp.306-315

2010

DOI: https://doi.org/10.1016/j.bbi.2009.10.011

Handle:

https://hdl.handle.net/2376/114060

PMCID: PMC2818367

PMID: 19861156

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https://doi.org/10.1016/j.bbi.2009.10.011View

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Abstract

Virus

Sickness behavior

Acute phase response

DsRNA

Body weight changes

Toll-like receptor 3

Influenza

Sleep changes

Locomotor activity

Hypothermia

Certain sickness behaviors occur consistently in influenza-infected humans and mice. These include body temperature changes, somnolence, and anorexia. Several cytokines serve as mediators of the influenza acute phase response (APR), including these sickness behaviors, and one likely inducer of these cytokines is dsRNA produced during viral replication. TLR3 is known to be one of the host cellular components capable of recognizing dsRNA and activating cytokine synthesis. To determine the role of TLR3-detected viral dsRNA in the causation of viral symptoms, TLR3-deficient mice (TLR3 knockouts, or KOs) were infected with a marginally-lethal dose of mouse-adapted X-31 influenza virus. TLR3 KOs and their wild-type (WT) controls were monitored for baseline body temperature, locomotor activity, and sleep profiles prior to infection. Both mouse strains were then infected and monitored for changes in these sickness behaviors plus body weight changes and mortality for up to 14 days post-infection. Consistent with the observations that influenza pathology is reduced in TLR3 KOs, we showed that hypothermia after post-infection day 5 and the total loss of body weight were attenuated in the TLR3 KOs. Sleep changes characteristic of this infection model [particularly increased non-rapid-eye-movement sleep (NREMS)] were also attenuated in TLR3 KOs and returned to baseline values more rapidly. Locomotor activity suppression was similar in both strains. Therefore virus-associated dsRNA detected by TLR3 appears to play a substantial role in mediating several aspects of the influenza syndrome in mice.

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Title: Attenuation of the influenza virus sickness behavior in mice deficient in Toll-like receptor 3
Creators: Jeannine A Majde - Department of VCAPP, College of Veterinary Medicine, Washington State University, Pullman, WA 99164-6520, USA
Levente Kapás - WWAMI Medical Education Program, Washington State University, Spokane, WA 99210-1495, USA
Stewart G Bohnet - Department of VCAPP, College of Veterinary Medicine, Washington State University, Pullman, WA 99164-6520, USA
Alok De - Department of Obstetrics and Gynecology, University of Missouri-Kansas City School of Medicine, Kansas City, MO 64108, USA
James M Krueger - Department of VCAPP, College of Veterinary Medicine, Washington State University, Pullman, WA 99164-6520, USA
Publication Details: Brain, behavior, and immunity, Vol.24(2), pp.306-315
Academic Unit: Biomedical Sciences, Department of; Integrative Physiology and Neuroscience, Department of
Publisher: Elsevier Inc
Identifiers: 99900547667201842
Language: English
Resource Type: Journal article