EBV Study Sheds Light on Immune Activation

Epstein-Barr virus (EBV) was discovered by Michael Epstein and Yvonne Barr in 1964. EBV causes or has been implicated in a number of human diseases. More than 90 percent of people have been infected with EBV during childhood, but these infections are often without symptoms and disease. However, when EBV infects adolescents and adults, it’s more likely to cause disease, such as infectious mononucleosis (IM).

While EBV infection hasn’t been causally linked to CFS, we know that about 5 to 10 percent of people with IM following EBV infection will not recover after six months and will develop CFS. We also know that the severity of the IM during the initial stages of the EBV infection is the greatest predictor for developing CFS. Unfortunately, we don’t yet know what it is about the severity of the acute EBV infection that puts a person at risk for CFS.

A recent paper published in the Journal of Affective Disorders identifies pathways and biomarkers that correlate with fatigue and symptoms of chronic active EBV infection. Because of the known connections between EBV, IM and CFS, chronic active EBV infection (CAEBV) may be a useful model for understanding the chronic immune activation and the pathophysiology of CFS.

A person sick with IM recovers when EBV-specific immunity develops. However, a subset of people develops CAEBV, which is characterized by chronic or recurrent IM, unusual patterns of antibodies to the virus, severe fatigue and impaired quality of life. Chronic immune activation features similar characteristics, and the authors proposed that tryptophan metabolism—a process necessary for serotonin production and proper immune function—might be involved.

In the investigation described in the paper, 20 people with chronic active EBV infection and 10 healthy age-matched controls were studied. Those with chronic active EBV
infection were examined at four and eight months.

Tryptophan metabolism was measured in each person. Investigators also measured EBV viral DNA and serum neopterin, which is a marker of cellular immune system activation.

The investigators found that the CAEBV patients with detectable EBV viral DNA had significantly higher serum neopterin and lower tryptophan levels than CAEBV patients without EBV viral DNA. Healthy controls did not show this relationship between neopterin and tryptophan. In addition, tryptophan degradation was aggravated in CAEBV patients with severe fatigue.

Tryptophan is one of the least abundant essential amino acids, yet it’s involved in a number of biological functions, including the immune response. The results of this study show that increased tryptophan degradation is associated with cell-mediated immune activation. This disturbance in tryptophan metabolism may explain the fatigue experienced by people with CAEBV, making CAEBV a useful model for understanding the chronic immune activation and pathophysiology of CFS.

Bellmann-Weiler R, Schroecksnadel K, Holzer C, Larcher C, Fuchs D, Weiss G. IFN-gamma mediated pathways in patients with fatigue and chronic active Epstein-Barr virus-infection. J Affect Disord. 2008 May;108(1-2):171-6.
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