Chronic Physical Stress Does Not Interact with Epstein-Barr Virus (EBV)-Encoded Dutpase to Alter the Sickness Response

Taryn G. Aubrecht^1*, Zachary M. Weil¹, Bachir Abi Salloum¹, Maria Eugenia Ariza², Marshall Williams², Brenda Reader³, Ronald Glaser^2,3, John Sheridan^3,4, Randy J. Nelson¹

¹Departments of Neuroscience, The Ohio State University, Columbus, OH, USA.
²Molecular Virology, Immunology & Medical Genetics, The Ohio State University, Columbus, OH, USA.
³Institute of Behavioral Medicine Research, Wexner Medical Center, Comprehensive Cancer Center, The Ohio State University, Columbus, OH, USA.
⁴Division of Biosciences, College of Dentistry, The Ohio State University, Columbus, OH, USA.

DOI: 10.4236/jbbs.2015.511049                

Abstract

Most adult humans have been infected with Epstein-Barr virus (EBV), which is thought to contribute to the development of chronic fatigue syndrome. Stress is known to influence the immune system and can exacerbate the sickness response. Although a role for psychological stress in the sickness response, particularly in combination with EBV-encoded deoxyuridine triphosphate nucleotidohydrolase (dUTPase) has been established, and the role of physical stressors in these interactions remains unspecified. In this study, we seek to determine the interaction of chronic physical (swim) stress and EBV-encoded dUTPase injection. We hypothesize that a chronic physical stressor will exacerbate the sickness response following EBV-encoded dUTPase injection. To test this hypothesis mice receive daily injections of EBV-encoded dUTPase or vehicle and are subjected to 15 min of swim stress each day for 14 days or left unmanipulated. On the final evening of injections mice undergo behavioral testing. EBV-encoded dUTPase injection alone produces some sickness behaviors. The physical swimming stress does not alter the sickness response.

Keywords

Epstein-Barr Virus, Swim Stress, Sickness Response

Conflicts of Interest

The authors declare no conflicts of interest.

References

[1]	Evengard, B. and Klimas, N. (2002) Chronic Fatigue Syndrome. Drugs, 62, 2433-2446. http://dx.doi.org/10.2165/00003495-200262170-00003
[2]	Loebel, M., Strohschein, K., Giannini, C., Koelsch, U., Bauer, S., Doebis, C., Thomas, S., Unterwalder, N., von Baehr, V., Reinke, P., Knops, M., Hanitsch, L.G., Meisel, C., Volk, H.D. and Scheibenbogen, C. (2014) Deficient EBV-Specific B- and T-Cell Response in Patients with Chronic Fatigue Syndrome. PLoS ONE, 9, e85387. http://dx.doi.org/10.1371/journal.pone.0085387
[3]	Lerner, A.M., Ariza, M.E., Williams, M., Jason, L., Beqaj, S., Fitzgerald, J.T., Lemeshow, S. and Glaser, R. (2012) Antibody to Epstein-Barr Virus Deoxyuridine Triphosphate Nucleotidohydrolase and Deoxyribonucleotide Polymerase in a Chronic Fatigue Syndrome Subset. PLoS ONE, 7, e47891. http://dx.doi.org/10.1371/journal.pone.0047891
[4]	Huang, Y., Henry, C.J., Dantzer, R., Johnson, R.W. and Godbout, J.P. (2008) Exaggerated Sickness Behavior and Brain Proinflammatory Cytokine Expression in Aged Mice in Response to Intracerebro-ventricular Lipopolysaccharide. Neurobiol Aging, 29, 1744-1753. http://dx.doi.org/10.1016/j.neurobiolaging.2007.04.012
[5]	Carlton, E.D., Demas, G.E. and French, S.S. (2012) Leptin, a Neuroendocrine Mediator of Immune Responses, Inflammation, and Sickness Behaviors. Hormones and Behavior, 62, 272-279. http://dx.doi.org/10.1016/j.yhbeh.2012.04.010
[6]	Glaser, R., Pearson, G.R., Bonneau, R.H., Esterling, B.A., Atkinson, C. and Kiecolt-Glaser, J.K. (1993) Stress and the Memory T-Cell Response to the Epstein-Barr Virus in Healthy Medical Students. Health Psychology, 12, 435-442. http://dx.doi.org/10.1037/0278-6133.12.6.435
[7]	Freeman, M.L., Sheridan, B.S., Bonneau, R.H. and Hendricks, R.L. (2007) Psychological Stress Compromises CD8+ T Cell Control of Latent Herpes Simplex Virus Type 1 Infections. Journal of Immunology, 179, 322-328. http://dx.doi.org/10.4049/jimmunol.179.1.322
[8]	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
[9]	Barnum, C.J., Pace, T.W., Hu, F., Neigh, G.N. and Tansey, M.G. (2012) Psychological Stress in Adolescent and Adult Mice Increases Neuroinflammation and Attenuates the Response to LPS Challenge. Journal of Neuroinflammation, 9, 9. http://dx.doi.org/10.1186/1742-2094-9-9
[10]	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
[11]	Padgett, D.A., Hotchkiss, A.K., Pyter, L.M., Nelson, R.J., Yang, E., Yeh, P.E., Litsky, M., Williams, M. and Glaser, R. (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
[12]	Mowlds, P., Barron, A. and Kavanagh, K. (2008) Physical Stress Primes the Immune Response of Galleria mellonella Larvae to Infection by Candida albicans. Microbes Infection, 10, 628-634. http://dx.doi.org/10.1016/j.micinf.2008.02.011
[13]	Oishi, K., Nishio, N., Konishi, K., Shimokawa, M., Okuda, T., Kuriyama, T. and Machida, K. (2003) Differential Effects of Physical and Psychological Stressors on Immune Functions of Rats. Stress, 6, 33-40. http://dx.doi.org/10.1080/1025389031000101330
[14]	Bowers, S.L., Bilbo, S.D., Dhabhar, F.S. and Nelson, R.J. (2008) Stressor-Specific Alterations in Corticosterone and Immune Responses in Mice. Brain, Behavior, and Immunity, 22, 105-113. http://dx.doi.org/10.1016/j.bbi.2007.07.012
[15]	Glaser, R., Litsky, M.L., Padgett, D.A., Baiocchi, R.A., Yang, E.V., Chen, M., Yeh, P.E., Green-Church, K.B., Caligiuri, M.A. and Williams, M.V. (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
[16]	Bilbo, S.D., Drazen, D.L., Quan, N., He, L. and Nelson, R.J. (2002) Short Day Lengths Attenuate the Symptoms of Infection in Siberian Hamsters. Proceedings of the Royal Society of London, Series B: Biological Sciences, 269, 447-454. http://dx.doi.org/10.1098/rspb.2001.1915
[17]	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
[18]	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
[19]	Deak, T., Bellamy, C. and D’Agostino, L.G. (2003) Exposure to Forced Swim Stress Does Not Alter Central Production of IL-1. Brain Research, 972, 53-63. http://dx.doi.org/10.1016/S0006-8993(03)02485-5
[20]	Guzzo, C., Ayer, A., Basta, S., Banfield, B.W. and Gee, K. (2012) IL-27 Enhances LPS-Induced Proinflammatory Cytokine Production via Upregulation of TLR4 Expression and Signaling in Human Monocytes. The Journal of Immunology, 188, 864-873. http://dx.doi.org/10.4049/jimmunol.1101912
[21]	Silverman, M.N., Mukhopadhyay, P., Belyavskaya, E., Tonelli, L.H., Revenis, B.D., Doran, J.H., Ballard, B.E., Tam, J., Pacher, P. and Sternberg, E.M. (2013) Glucocorticoid Receptor Dimerization Is Required for Proper Recovery of LPS-Induced Inflammation, Sickness Behavior and Metabolism in Mice. Molecular Psychiatry, 18, 1006-1017. http://dx.doi.org/10.1038/mp.2012.131
[22]	Martin, S.A., Pence, B.D., Greene, R.M., Johnson, S.J., Dantzer, R., Kelley, K.W. and Woods, J.A. (2013) Effects of Voluntary Wheel Running on LPS-Induced Sickness Behavior in Aged Mice. Brain, Behavior, and Immunity, 29, 113-123. http://dx.doi.org/10.1016/j.bbi.2012.12.014
[23]	Martin, S.A., Dantzer, R., Kelley, K.W. and Woods, J.A. (2014) Voluntary Wheel Running Does Not Affect Lipopolysaccharide-Induced Depressive-Like Behavior in Young Adult and Aged Mice. Neuroimmunomodulation, 21, 52-63. http://dx.doi.org/10.1159/000356144
[24]	Dayas, C.V., Buller, K.M., Crane, J.W., Xu, Y. and Day, T.A. (2001) Stressor Categorization: Acute Physical and Psychological Stressors Elicit Distinctive Recruitment Patterns in the Amygdala and in Medullary Noradrenergic Cell Groups. European Journal of Neuroscience, 14, 1143-1152. http://dx.doi.org/10.1046/j.0953-816x.2001.01733.x
[25]	Shu, J., Stevenson, J.R. and Zhou, X. (1993) Modulation of Cellular Immune Responses by Cold Water Swim Stress in the Rat. Developmental & Comparative Immunology, 17, 357-371. http://dx.doi.org/10.1016/0145-305X(93)90007-D
[26]	Aubrecht, T.G., Salloum, B.A., Ariza, M.E., Williams, M., Reader, B., Glaser, R., Sheridan, J. and Nelson, R.J. (2014) Restraint Induces Sickness Responses Independent of Injection with Epstein-Barr Virus (EBV)-Encoded dUTPase. Journal of Behavioral and Brain Science, 4, 491-505. http://dx.doi.org/10.4236/jbbs.2014.411049