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.
Highlights
Chronic fatigue syndrome (CFS) is characterized by severe fatigue, myalgia, lymphadenopathy, sore throat, stress, and depression [1]
To determine the short-term duration of Epstein-Barr virus (EBV)-encoded deoxyuridine triphosphate nucleotidohydrolase (dUTPase) injections required to elicit a change in anxiety- and depressive-like behaviors and the sickness response, as well as how a psychological stressor alters the sickness response, mice were injected with EBV-encoded dUTPase for one or three days and restrained for 3 h each day
20 μg EBV-encoded dUTPase injections induced a sickness response in mice; temperature was measured twice daily, but EBV-encoded dUTPase-induced increases in body temperature did not occur until the fifth day and significant temperature differences were intermittent through the remainder of the 14 days of injections [15]
Summary
Chronic fatigue syndrome (CFS) is characterized by severe fatigue, myalgia, lymphadenopathy, sore throat, stress, and depression [1] This constellation of symptoms is termed “sickness response”, and is conserved across many mammalian species and functions to aid in recovery from illness [2]. Treatment of adrenal intact rats with a glucocorticoid receptor antagonist increases plasma levels of IL-6 and fever compared to vehicle treated animals [10]. These data suggest that glucocorticoids are involved in inhibitory feedback to control the immune response and contribute to the development of sickness behavior
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