Share This Article:

Restraint Induces Sickness Responses Independent of Injection with Epstein-Barr Virus (EBV)-Encoded dUTPase

Abstract Full-Text HTML XML Download Download as PDF (Size:3184KB) PP. 491-505
DOI: 10.4236/jbbs.2014.411049    3,439 Downloads   3,802 Views   Citations

ABSTRACT

Most adult humans have been infected by Epstein-Barr virus (EBV), a putative cause of chronic fatigue syndrome, and carry latent EBV. The EBV-encoded dUTPase can induce sickness responses in mice and chronic stress exacerbates this response. Because individuals often adapt to chronic stress, we tested the hypothesis that acute restraint stress would potentiate these sickness responses elicited by EBV-encoded dUTPase. Male CD-1 mice were injected daily for one or three days with either saline or EBV-encoded dUTPase. Additionally, mice from each condition were either restrained for three hours daily or left undisturbed during the light phase when mice are inactive. Restraint decreased weight gain during the one- and three-day experiments. Restraint in saline injected mice increased anxiety-like behavior in the open field during the three-day experiment. There were no behavioral differences during the one-day experiment. Restraint stress had no effect when experienced acutely on one day, but did produce a sickness response after three days of exposure regardless of saline or dUTPase injection. In contrast to the effects of chronic stress and EBV-encoded dUTPase on the sickness response, acute stress did not affect sickness responses in association with EBV-encoded dUTPase. Thus, dUTPase does not appear to provoke the same sickness responses after acute stress as compared to chronic stress.

Conflicts of Interest

The authors declare no conflicts of interest.

Cite this paper

Aubrecht, T. , Salloum, B. , Ariza, M. , Williams, M. , Reader, B. , Glaser, R. , Sheridan, J. and Nelson, R. (2014) Restraint Induces Sickness Responses Independent of Injection with Epstein-Barr Virus (EBV)-Encoded dUTPase. Journal of Behavioral and Brain Science, 4, 491-505. doi: 10.4236/jbbs.2014.411049.

References

[1] Evengard, B. and Klimas, N. (2002) Chronic Fatigue Syndrome: Probable Pathogenesis and Possible Treatments. Drugs, 62, 2433-2446.
http://dx.doi.org/10.2165/00003495-200262170-00003
[2] Dantzer, R. and Kelley, K.W. (2007) Twenty Years of Research on Cytokine-Induced Sickness Behavior. Brain, Behavior, and Immunity, 21, 153-160.
http://dx.doi.org/10.1016/j.bbi.2006.09.006
[3] Glaser, R. and Kiecolt-Glaser, J.K. (2005) Stress-Induced Immune Dysfunction: Implications for Health. Nature Reviews Immunology, 5, 243-251.
http://dx.doi.org/10.1038/nri1571
[4] Dhabhar, F.S. and McEwen, B.S. (1997) Acute Stress Enhances While Chronic Stress Suppresses Cell-Mediated Immunity in Vivo: A Potential Role for Leukocyte Trafficking. Brain, Behavior, and Immunity, 11, 286-306.
http://dx.doi.org/10.1006/brbi.1997.0508
[5] Padgett, D.A. and Glaser, R. (2003) How Stress Influences the Immune Response. Trends in Immunology, 24, 444-448.
http://dx.doi.org/10.1016/S1471-4906(03)00173-X
[6] Hennessy, M.B., Deak, T. and Schiml-Webb, P.A. (2001) Stress-Induced Sickness Behaviors: An Alternative Hypothesis for Responses during Maternal Separation. Developmental Psychobiology, 39, 76-83.
http://dx.doi.org/10.1002/dev.1031
[7] Sapolsky, R.M., Romero, L.M. and Munck, A.U. (2000) How Do Glucocorticoids Influence Stress Responses? Integrating Permissive, Suppressive, Stimulatory, and Preparative Actions. Endocrine Reviews, 21, 55-89.
[8] Zhou, D., Kusnecov, A.W., Shurin, M.R., DePaoli, M. and Rabin, B.S. (1993) Exposure to Physical and Psychological Stressors Elevates Plasma Interleukin 6: Relationship to the Activation of Hypothalamic-Pituitary-Adrenal Axis. Endocrinology, 133, 2523-2530.
[9] LeMay, L.G., Vander, A.J. and Kluger, M.J. (1990) The Effects of Psychological Stress on Plasma Interleukin-6 Activity in Rats. Physiology & Behavior, 47, 957-961.
http://dx.doi.org/10.1016/0031-9384(90)90024-X
[10] Morrow, L.E., McClellan, J.L., Conn, C.A. and Kluger, M.J. (1993) Glucocorticoids alter Fever and IL-6 Responses to Psychological Stress and to Lipopolysaccharide. American Journal of Physiology, 264, R1010-R1016.
[11] Glaser, R., Litsky, M.L., Padgett, D.A., Baiocchi, R.A., Yang, E.V., Chen, M., et al. (2006) EBV-Encoded dUTPase Induces Immune Dysregulation: Implications for the Pathophysiology of EBV-Associated Disease. Virology, 346, 205-218.
http://dx.doi.org/10.1016/j.virol.2005.10.034
[12] Ariza, M.E., Glaser, R., Kaumaya, P.T., Jones, C. and Williams, M.V. (2009) The EBV-Encoded dUTPase Activates NF-κB through the TLR2 and MyD88-Dependent Signaling Pathway. Journal of Immunology, 182, 851-859.
http://dx.doi.org/10.4049/jimmunol.182.2.851
[13] Waldman, W.J., Williams Jr., M.V., Lemeshow, S., Binkley, P., Guttridge, D., Kiecolt-Glaser, J.K., et al. (2008) Epstein-Barr Virus-Encoded dUTPase Enhances Proinflammatory Cytokine Production by Macrophages in Contact with Endothelial Cells: Evidence for Depression-Induced Atherosclerotic Risk. Brain, Behavior, and Immunity, 22, 215-223.
http://dx.doi.org/10.1016/j.bbi.2007.07.007
[14] Ariza, M.E., Rivailler, P., Glaser, R., Chen, M. and Williams, M.V. (2013) Epstein-Barr Virus Encoded dUTPase Containing Exosomes Modulate Innate and Adaptive Immune Responses in Human Dendritic Cells and Peripheral Blood Mononuclear Cells. PLoS ONE, 8, e69827.
http://dx.doi.org/10.1371/journal.pone.0069827
[15] Padgett, D.A., Hotchkiss, A.K., Pyter, L.M., Nelson, R.J., Yang, E., Yeh, P.E., et al. (2004) Epstein-Barr Virus-Encoded dUTPase Modulates Immune Function and Induces Sickness Behavior in Mice. Journal of Medical Virology, 74, 442-448.
http://dx.doi.org/10.1002/jmv.20196
[16] De La Garza II, R. (2005) Endotoxin- or Pro-Inflammatory Cytokine-Induced Sickness Behavior as an Animal Model of Depression: Focus on Anhedonia. Neuroscience & Biobehavioral Reviews, 29, 761-770.
http://dx.doi.org/10.1016/j.neubiorev.2005.03.016
[17] Yirmiya, R., Pollak, Y., Morag, M., Reichenberg, A., Barak, O., Avitsur, R., et al. (2000) Illness, Cytokines, and Depression. Annals of the New York Academy of Sciences, 917, 478-487.
http://dx.doi.org/10.1111/j.1749-6632.2000.tb05412.x
[18] Aubrecht, T.G., Weil, Z.M., Ariza, M.E., Williams, M., Reader, B.F., Glaser, R., Sheridan, J.F. and Nelson, R.J. (2014) Epstein-Barr Virus (EBV)-Encoded dUTPase and Chronic Restraint Induce Impaired Learning and Memory and Sickness Responses. Physiology & Behavior, 137, 18-24.
http://dx.doi.org/10.1016/j.physbeh.2014.07.001
[19] Williams, M.V. and Pollack, J.D. (1985) Pyrimidine Deoxyribonucleotide Metabolism in Acholeplasma Laidlawii B-PG9. Journal of Bacteriology, 161, 1029-1033.
[20] Nyman, P.O. (2001) Introduction. dUTPases. Current Protein & Peptide Science, 2, 277-285.
http://dx.doi.org/10.2174/1389203013381071
[21] el-Hajj, H.H., Zhang, H. and Weiss, B. (1988) Lethality of a Dut (Deoxyuridine Triphosphatase) Mutation in Escherichia coli. Journal of Bacteriology, 170, 1069-1075.
[22] Gadsden, M.H., McIntosh, E.M., Game, J.C., Wilson, P.J. and Haynes, R.H. (1993) dUTP Pyrophosphatase Is an Essential Enzyme in Saccharomyces cerevisiae. EMBO Journal, 12, 4425-4431.
[23] Baldo, A.M. and McClure, M.A. (1999) Evolution and Horizontal Transfer of dUTPase-Encoding Genes in Viruses and Their Hosts. Journal of Virology, 73, 7710-7721.
[24] McGeoch, D.J., Cook, S., Dolan, A., Jamieson, F.E. and Telford, E.A. (1995) Molecular Phylogeny and Evolutionary Timescale for the Family of Mammalian Herpesviruses. Journal of Molecular Biology, 247, 443-458.
http://dx.doi.org/10.1006/jmbi.1995.0152
[25] Tarbouriech, N., Buisson, M., Seigneurin, J.M., Cusack, S. and Burmeister, W.P. (2005) The Monomeric dUTPase from Epstein-Barr Virus Mimics Trimeric dUTPases. Structure, 13, 1299-1310.
http://dx.doi.org/10.1016/j.str.2005.06.009
[26] Davison, A.J. and Stow, N.D. (2005) New Genes from Old: Redeployment of dUTPase by Herpesviruses. Journal of Virology, 79, 12880-12892.
http://dx.doi.org/10.1128/JVI.79.20.12880-12892.2005
[27] Camacho, A., Arrebola, R., Pena-Diaz, J., Ruiz-Perez, L.M. and Gonzalez-Pacanowska, D. (1997) Description of a Novel Eukaryotic Deoxyuridine 5'-Triphosphate Nucleotidohydrolase in Leishmania Major. Biochemical Journal, 325, 441-447.
[28] Camacho, A., Hidalgo-Zarco, F., Bernier-Villamor, V., Ruiz-Perez, L.M. and Gonzalez-Pacanowska, D. (2000) Properties of Leishmania Major dUTP Nucleotidohydrolase, a Distinct Nucleotide-Hydrolysing Enzyme in Kinetoplastids. Biochemical Journal, 346, 163-168.
http://dx.doi.org/10.1042/0264-6021:3460163
[29] Bernier-Villamor, V., Camacho, A., Hidalgo-Zarco, F., Perez, J., Ruiz-Perez, L.M. and González-Pacanowska, D. (2002) Characterization of Deoxyuridine 5’-Triphosphate Nucleotidohydrolase from Trypanosoma cruzi. FEBS Letters, 526, 147-150.
http://dx.doi.org/10.1016/S0014-5793(02)03158-7
[30] Hill, F., Loakes, D. and Brown, D.M. (1998) Polymerase Recognition of Synthetic Oligodeoxyribonucleotides Incorporating Degenerate Pyrimidine and Purine Bases. Proceedings of the National Academy of Sciences of the United States of America, 95, 4258-4263.
http://dx.doi.org/10.1073/pnas.95.8.4258
[31] Parkhill, J., Wren, B.W., Mungall, K., Ketley, J.M., Churcher, C., Basham, D., et al. (2000) The Genome Sequence of the Food-Borne Pathogen Campylobacter jejuni Reveals Hyper-variable Sequences. Nature, 403, 665-668.
http://dx.doi.org/10.1038/35001088
[32] Dantzer, R., O’Connor, J.C., Freund, G.G., Johnson, R.W. and Kelley, K.W. (2008) From Inflammation to Sickness and Depression: When the Immune System Subjugates the Brain. Nature Reviews Neuroscience, 9, 46-56.
http://dx.doi.org/10.1038/nrn2297
[33] Junker, A.K. (2005) Epstein-Barr Virus. Pediatrics in Review, 26, 79-85.
http://dx.doi.org/10.1542/pir.26-3-79
[34] Swiergiel, A.H. and Dunn, A.J. (2007) Effects of Interleukin-1β and Lipopolysaccharide on Behavior of Mice in the Elevated Plus-Maze and Open Field Tests. Pharmacology Biochemistry and Behavior, 86, 651-659.
http://dx.doi.org/10.1016/j.pbb.2007.02.010
[35] Bauer, M.E., Perks, P., Lightman, S.L. and Shanks, N. (2001) Restraint Stress Is Associated with Changes in Glucocorticoid Immunoregulation. Physiology & Behavior, 73, 525-532.
http://dx.doi.org/10.1016/S0031-9384(01)00503-0
[36] Bedrosian, T.A., Fonken, L.K., Walton, J.C., Haim, A. and Nelson, R.J. (2010) Dim Light at Night Provokes Depression-Like Behaviors and Reduces CA1 Dendritic Spine Density in Female Hamsters. Psychoneuroendocrinology, 36, 1062-1069.
http://dx.doi.org/10.1016/j.psyneuen.2011.01.004
[37] Steru, L., Chermat, R., Thierry, B. and Simon, P. (1985) The Tail Suspension Test: A New Method for Screening Antidepressants in Mice. Psychopharmacology, 85, 367-370.
http://dx.doi.org/10.1007/BF00428203
[38] Hanke, M.L., Powell, N.D., Stiner, L.M., Bailey, M.T. and Sheridan, J.F. (2012) Beta Adrenergic Blockade Decreases the Immunomodulatory Effects of Social Disruption Stress. Brain, Behavior, and Immunity, 26, 1150-1159.
http://dx.doi.org/10.1016/j.bbi.2012.07.011
[39] Mariani, T.J., Budhraja, V., Mecham, B.H., Gu, C.C., Watson, M.A. and Sadovsky, Y. (2003) A Variable Fold Change Threshold Determines Significance for Expression Microarrays. FASEB Journal, 17, 321-323.
[40] Griffin, B.E. (2000) Epstein-Barr Virus (EBV) and Human Disease: Facts, Opinions and Problems. Mutation Research, 462, 395-405.
http://dx.doi.org/10.1016/S1383-5742(00)00028-4
[41] Weinert, D. and Waterhouse, J. (1998) Diurnally Changing Effects of Locomotor Activity on Body Temperature in Laboratory Mice. Physiology & Behavior, 63, 837-843.
http://dx.doi.org/10.1016/S0031-9384(97)00546-5
[42] Mercado, A.M., Padgett, D.A., Sheridan, J.F. and Marucha, P.T. (2002) Altered Kinetics of IL-1α, IL-1β, and KGF-1 Gene Expression in Early Wounds of Restrained Mice. Brain, Behavior, and Immunity, 16, 150-162.
http://dx.doi.org/10.1006/brbi.2001.0623
[43] Munhoz, C.D., Lepsch, L.B., Kawamoto, E.M., Malta, M.B., Lima, S., et al. (2006) Chronic Unpredictable Stress Exacerbates Lipopolysaccharide-Induced Activation of Nuclear Factor-κB in the Frontal Cortex and Hippocampus via Glucocorticoid Secretion. Journal of Neuroscience, 26, 3813-3820.
http://dx.doi.org/10.1523/JNEUROSCI.4398-05.2006
[44] Gibb, J., Al-Yawer, F. and Anisman, H. (2013) Synergistic and Antagonistic Actions of Acute or Chronic Social Stressors and an Endotoxin Challenge Vary over Time Following the Challenge. Brain, Behavior, and Immunity, 28, 149-158.
http://dx.doi.org/10.1016/j.bbi.2012.11.004
[45] Johnson, J.D., O’Connor, K.A., Hansen, M.K., Watkins, L.R. and Maier, S.F. (2003) Effects of Prior Stress on LPS-Induced Cytokine and Sickness Responses. American Journal of Physiology-Regulatory, Integrative and Comparative Physiology, 284, R422-R432.
[46] Bassi, G.S., Kanashiro, A., Santin, F.M., de Souza, G.E., Nobre, M.J. and Coimbra, N.C. (2012) Lipopolysaccharide-Induced Sickness Behaviour Evaluated in Different Models of Anxiety and Innate Fear in Rats. Basic & Clinical Pharmacology & Toxicology, 110, 359-369.
http://dx.doi.org/10.1111/j.1742-7843.2011.00824.x
[47] Tanaka, S., Ide, M., Shibutani, T., Ohtaki, H., Numazawa, S., Shioda, S. and Yoshida, T. (2006) Lipopolysaccharide-Induced Microglial Activation Induces Learning and Memory Deficits without Neuronal Cell Death in Rats. Journal of Neuroscience Research, 83, 557-566.
http://dx.doi.org/10.1002/jnr.20752

  
comments powered by Disqus

Copyright © 2018 by authors and Scientific Research Publishing Inc.

Creative Commons License

This work and the related PDF file are licensed under a Creative Commons Attribution 4.0 International License.