Abortive lytic Epstein–Barr virus replication in tonsil-B lymphocytes in infectious mononucleosis and a subset of the chronic fatigue syndrome
A Martin Lerner,1 Safedin Beqaj2
1Department of Medicine, Oakland University William Beaumont School of Medicine, Rochester, MI, USA; 2Pathology Inc, Torrance, CA, USA
Abstract: A systematic 2001–2007 review of 142 chronic fatigue syndrome (CFS) patients identified 106 CFS patients with elevated serum IgG antibodies to the herpesviruses Epstein–Barr virus (EBV), cytomegalovirus, or human herpesvirus (HHV) 6 in single or multiple infections, with no other co-infections detected. We named these 106 patients group-A CFS. Eighty-six of these 106 group-A CFS patients (81%) had elevated EBV early antibody, early antigen (diffuse), serum titers. A small group of six patients in the group-A EBV subset of CFS, additionally, had repetitive elevated-serum titers of antibody to the early lytic replication-encoded proteins, EBV dUTPase, and EBV DNA polymerase. The presence of these serum antibodies to EBV dUTPase and EBV DNA polymerase indicated EBV abortive lytic replication in these 6 CFS patients. None of 20 random control people (age- and sex-matched, with blood drawn at a commercial laboratory) had elevated serum titers of antibody to EBV dUTPase or EBV DNA polymerase (P < 0.01). This finding needs verification in a larger group of EBV CFS subset patients, but if corroborated, it may represent a molecular marker for diagnosing the EBV subset of CFS. We review evidence that EBV abortive lytic replication with unassembled viral proteins in the blood may be the same in infectious mononucleosis (IM) and a subset of CFS. EBV-abortive lytic replication in tonsil plasma cells is dominant in IM. No complete lytic virion is in the blood of IM or CFS patients. Complications of CFS and IM include cardiomyopathy and encephalopathy. Circulating abortive lytic-encoded EBV proteins (eg, EBV dUTPase, EBV DNA polymerase, and others) may be common to IM and CFS. The intensity and duration of the circulating EBV-encoded proteins might differentiate the IM and EBV subsets of CFS. Abortive lytic replication may be a pathogenic mechanism for EBV disease. EBV (HHV4) is a gamma herpesvirus composed of dsDNA about 170 Kb in length. For this discussion, there are early genes (including expressions of encoded proteins EBV dUTPase, DNA polymerase, and nuclear proteins) and late genes (including expressions of capsid and membrane proteins). Abortive infection infers incomplete virion expressions of either early or late proteins, but the virion is incomplete. The lytic virus infers a complete virion. The pathologic consequences of EBV abortive replication are currently being investigated by authors.
Keywords: Epstein–Barr virus, chronic fatigue syndrome, subset chronic fatigue syndrome, abortive lytic replication
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