Depression and post-viral fatigue: role of cytokines

University Of Michigan At Ann Arbor, Ann Arbor MI

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Abstract

[unreadable] DESCRIPTION (provided by applicant): Fatigue is a common complaint in society and can greatly affect quality of life and productivity. Recent studies suggest strong interactions between infectious challenge, the immune response, impaired night-time sleep, and daytime fatigue. Specifically, human gammaherpesviruses (GHVs), such as Epstein Barr virus (EBV), have been associated with chronic fatigue. It is estimated that 95% of all adults have been infected with EBV. During EBV infection, and in patients with chronic fatigue, cytokines that induce fatigue and alter sleep, such as IL-1, IL-6, IL-10 and IFN-gamma are chronically elevated. However systematic studies to elucidate links between these cytokines and resulting sleep changes and fatigue resulting from EBV infection have not been done. Murine GHV (MuGHV)-68 has been used as a model of human GHV due to the similarity of the immune response, viral genetics, ability to cause an active infection, and subsequent development of life-long latency 44. Using mice infected with MuGHV, we will determine potential mechanisms mediating fatigue during chronic viral infection. We hypothesize that mice infected with MuGHV will become fatigued, and that cytokines are mediators of these behavioral responses. We will use the following aims to test this hypothesis: Determine the impact of behavioral responses of mice to infection with MuGHV-68; determine the effects of a secondary immune challenge during the latent phase of infection of mice with MuGHV-68: determine the role of specific cytokines as mediators in response to MuGHV infection. [unreadable] [unreadable] [unreadable]