Antibodies to herpesvirus dUTPase a potential biomarker for Gulf War Illness and CFS

Herpesvirus-encoded dUTPases can trigger modulation of genes involved in chronic inflammation, T-cell function, and neurotransmitter function. A group from Ohio State University led by Maria Aziza, PhD, found that antibodies to HHV-6 and VZV dUTPases were significantly elevated in Gulf War Illness (GWI) patients compared to controls. EBV dUTPase antibodies were elevated in Chronic Fatigue Syndrome (CFS) patients. Also, the CFS and GWI groups exhibited increased autoimmunity; 15% of CFS and 39% of GWI patients had autoantibodies against human dUTPase, compared to 4.7% among controls.

As the herpesvirus dUTPases are only expressed during viral replication or active “abortive” infection, they are a good indicator of viral activity. 49% of CFS patients co-expressed antibodies to both HHV-6 and EBV dUTPases, and 55% were positive for HHV-6. 31% expressed anti-human (autoantibodies) and anti-HHV-dUTPase antibodies together. Similarly, the GWI cohort exhibited a significant increase in anti-HHV-6, anti-VZV, and anti-human dUTPase antibodies compared to controls.

The high levels of anti-herpesvirus and anti-human dUTPase antibodies suggest to the authors that immune responses are significantly altered in CFS and GWI patients, with a possible loss of immune competence. They note that the dUTPases produced during herpesvirus reactivation in these already compromised individuals could contribute to the immune potentiation of the disease process. Gulf War Illness is a chronic disorder causing fatigue, muscle pain and cognitive problems in approximately 250,000 of the US veterans who served in the 1991 Gulf War. CFS, affects 1-2.4 million people in the US with symptoms that include persistent fatigue, non-restorative sleep, cognitive impairment and exercise intolerance.

Maria Ariza, PhD of Ohio State University

Maria Ariza, PhD of Ohio State University

While herpesviruses have been investigated for their role in ME/CFS, very little research has been done on their role in GWI, which has several symptoms in common with CFS, including fatigue, neurocognitive dysfunction, and immune activation. Moreover, patients with GWI experience higher rates of CFS than the general population. As a result, this multi-institutional team set out to determine whether herpesviruses are involved in GWI and will continue to explore the mechanisms by which the HHV-6 and EBV dUTPases may contribute to the pathophysiological disturbances that occur in patients with CFS and GWI.

HHV-6 reactivates in response to stress and immune suppression, and reactivation causes delirium, cognitive dysfunction, and fatigue in transplant patients (Zerr 2011, Hill 2015). It has been proposed as a trigger for CFS (Komaroff 2006) and reactivates in approximately half of emergency room patients (Razonable 2002). HHV-6 also reactivates in response to drug allergies and chemical exposures; over 60% of extreme drug hypersensitivity cases are associated with HHV-6 reactivation (Tohyama 2007).

Read the full paper here: Halpin 2017.