Antiviral Pathway Deregulation of Chronic Fatigue Syndrome Induces Nitric Oxide Production in Immune Cells That Precludes a Resolution of the Inflammatory Response

AbstractChronic fatigue syndrome (CFS) is a poorly defined medical condition diagnosed by exclusion, which, besides severe chronic fatigue as the hallmark symptom, involves inflammatory and immune activation stigma. Although viral infections are not systematically found in CFS patients, the type I interferon antiviral pathway has been repeatedly shown to be activated in peripheral blood mononuclear cells (PBMC) of the most afflicted patients. An abnormal truncated form of ribonuclease L (37-kDa RNase L) is also found in the PBMC of CFS patients and this protein has been proposed as a biological marker for CFS. Recently, the levels of this abnormal protein have been significantly correlated to the extent of inflammatory symptoms displayed by CFS patients. We report here that active double-stranded RNA-dependent kinase (PKR) is expressed and activated in parallel to the presence of the 37-kDa RNase L and to an increase in nitric oxide production by immune cells. However, PKR upregulation results also in a s...