Fatal Epstein-Barr virus infection in a child with acute lymphoblastic leukemia in remission.

A 9-year-old white boy developed a fatal primary Epstein-Barr virus (EBV) infection while receiving chemotherapy for acute lymphoblastic leukemia in remission. Histopathological findings at the height of the proliferative phase of the illness were compatible with a virally induced hemophagocytic syndrome. The infection spontaneously converted to complete aplasia of the bone marrow and lymph nodes. Serological studies disclosed that the patient had no antibodies to EBV prior to the infection, but during the acute phase he showed a spectrum and titers of antibodies to EBV-specific antigens characteristic of a current primary EBV infection. A lymph node biopsy obtained 5 weeks after onset revealed Epstein-Barr nuclear antigen in approximately 50% of the cells. The boy's condition deteriorated rapidly, with disseminated candidiasis resulting in cardiorespiratory failure and death. Lymph nodes obtained at autopsy no longer contained Epstein-Barr nuclear antigen-positive cells.

Viruses and renal carcinoma of Rana pipiens. XV. The presence of virus-associated membrane antigen(s) on Lucké tumor cells.

Virus-specific antigens were detected in Lucké tumor cells by indirect immunofluorescence using antiserum prepared against Lucké herpesvirus. Intracellular fluorescence, both cytoplasmic and nuclear, was observed only in acetone:methanol-fixed tumor cells that contained herpesvirus detected by electron microscopy. The number of positive cells correlated well with the number of cells containing virus. In contrast, both virus-containing and virus-free cells exhibited membrane fluorescence when viable unfixed tumor cells were tested. A striking reduction in the number of membrane fluorescent cells was observed with an increase in the length of time that tumor cells were in primary culture. No reaction was observed with a variety of normal R. pipiens cells. Absorption of the antiserum with normal frog kidney tissue had no effect on the number of positive cells whereas absorption with virus-free tumor reduced the reaction; absorption with virus-containing tumor eliminated it. These findings provide the first demonstration that the Lucké herpesvirus genome resident in virus-free tumor cells expresses a virus-associated membrane antigen(s).

The presence of the Lucké herpesvirus genome in induced tadpole tumors and its oncogenicity: Koch-Henle postulates fulfilled.

Herpesvirus extracted from a naturally occurring frog renal carcinoma (Lucké tumor) induced virus-free Lucké tumors in developing frogs. Herpesvirus recovered from an induced tumor after incubation at low temperature of tumor fragments cultured in vitro was oncogenic when injected into developing frog embryos. With the exception of the "pure culture" requirement, this experiment fulfills Koch-Henle postulates for the identification of the causative agent of the Lucké tumor.

Nasopharyngeal carcinoma in American Children: Epstein-Barr virus-specific antibody titers and prognosis.

Seven American juvenile patients with undifferentiated or nonkeratinizing nasopharyngeal carcinoma (NPC) were examined serially for Epstein-Barr virus (EBV)-specific antibody spectra and titers in sera. At diagnosis, all showed antibody patterns characteristic of NPC: i.e., high titers of IgG antibodies to viral capsid antigen (VCA) and to the diffuse (D) component of the early antigen complex. Six patients had IgA antibodies to VCA, and four to the D component. In the patients who responded to therapy with complete and maintained remissions, the IgG antibodies to D and the IgA antibodies to VCA and D decreased to undetectable levels within 12 to 30 months. By contrast, of the four patients who responded only transiently to therapy, three showed substantial increases and one continuously high titers of IgG anti-D and IgA anti-VCA. The increases in antibody titers preceded clinical recognition of recurrent tumors by 1 to 6 months. Three of these patients have died and the fourth is alive with disease. These data indicate that American juvenile NPC does not differ from the adult disease observed anywhere in the World. They reaffirm the potential usefulness of EBV-specific serology in the diagnosis and prognosis of NPC and the monitoring of patients following therapy.

Antibody responses to Epstein-Barr virus-specific DNase in relation to the prognosis of juvenile patients with nasopharyngeal carcinoma.

We have examined serial sera from 17 juvenile patients with nasopharyngeal carcinoma (NPC) for their capacity to neutralize the activity of Epstein-Barr virus (EBV)-specific DNase. The results revealed that NPC patients who became long-term survivors (LTS) without evidence of the disease either never possessed significant levels of antibodies to the enzyme or showed a gradual decline in the number of EBV DNase units neutralized from an elevated level at diagnosis to an insignificant figure several years later. All the 10 LTS neutralized less than 4, and some neutralized less than 2 units of the enzyme 3 or more years after the initial diagnosis. In contrast, serial sera from juvenile patients who died of NPC neutralized over 10 and as many as 25 units of EBV DNase either persistently until death occurred or with transient declines during unmaintained remissions. Rises and declines in the neutralizing activity were, with few exceptions, accompanied by corresponding changes in the titers of IgA and IgG antibodies to EB viral capsid antigen and to the diffuse component of the early antigens. Although the number of juvenile NPC cases available for study was small, the observations suggest that the EBV DNase neutralization test may serve to provide information on the prognosis of the patients.