Viral Etiology of Diseases of the Hematopoietic System

Abstract

In 1968 the Epstein-Barr virus (EBV) was identified as the causal agent of infectious mononucleosis [4]. Eleven years later a number of questions still remain unresolved: 1) In which cells does the virus replicate? There is little doubt that specific cells of the oropharyngeal region support EBV replication since transforming virus may be recovered from the saliva of infected patients and from healthy virus carriers. Nevertheless, the exact site of virus replication has not been identified. Suggestive evidence has been obtained that epithelial cells, possibly derived from the nasopharyngeal region, support EBV replication [8]. 2) Which host factors determine the pathogenesis of EBV infection? A schematic outline of current concepts was presented earlier [13]. According to this model, after initial replication in nonlymphocytic cells the virus infects B-lymphocytes, which are transformed into lymphoblasts and express new surface properties. This in turn leads to a T-cell response directed against the transformed lymphocytes, which eventually should limit the course of the disease. Two lines of evidence supporting this view exist: EBV-transformed B-lymphoblasts are readily recovered from patients with infectious mononucleosis and grow indefinitely in tissue culture. Special chemical inductors permit the recovery of infectious EBV from such cultures [15]. Secondly, connatal or acquired T-cell deficiencies lead, upon EBV infection, to massive proliferation of transformed B-lymphoblasts resulting in a chronic and sometimes fatal infectious mononucleosis. An X-linked inherited immune defect described recently by Purtilo and co-workers [9], the X-linked lymphoproliferative syndrome, reveals this typical symptomatology upon EBV infection of patients. Other factors that may determine the course of the disease are presently unknown.