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Epstein-Barr Virus in the Bone Marrow of Patients with Aplastic Anemia

Bruce Baranski, MD; Gary Armstrong, BSMT; John T. Truman, MD; Gerald V. Quinnan Jr, MD; Stephen E. Straus, MD; and Neal S. Young, MD
[+] Article, Author, and Disclosure Information

Requests for Reprints: Neal S. Young, MD, Building 10, Room 7C103, National Institutes of Health, 9000 Rockville Pike, Bethesda, MD 20892.

Current Author Addresses: Dr. Baranski: Room H4/540 Clinical Sciences Center, University of Wisconsin, 600 Highland Avenue, Madison, WI 53792.

Mr. Armstrong: Building 29A, HFB-5000, 8800 Rockville Pike, Bethesda, MD 20892.

Dr. Truman: Department of Pediatrics, Morristown Memorial Hospital, 100 Madison Avenue, Morristown, NJ 07960.

Dr. Quinnan: Building 29, HFB-2, 8800 Rockville Pike, Bethesda, MD 20892.

Dr. Straus: Building 10, Room 11N-113, 9000 Rockville Pike, Bethesda, MD 20892.

Dr. Young: Building 10, Room 7C103, 9000 Rockville Pike, Bethesda,

Ann Intern Med. 1988;109(9):695-704. doi:10.7326/0003-4819-109-9-695
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Study Objective: To determine whether Epstein-Barr virus is present in the bone marrow of patients with aplastic anemia.

Design: Assay of fresh and fixed bone marrow specimens for Epstein-Barr virus using immunofluorescence for nuclear antigen, Southern analysis with an Epstein-Barr virus specific probe, and in-situ hybridization.

Setting: Governmental medical referral center.

Patients: Five patients were studied prospectively: three who previously had infectious mononucleosis, one with a recent viral pneumonitis, and one who was asymptomatic. Stored DNA samples from other patients with aplastic anemia were also screened.

Measurements and Main Results: Epstein-Barr virus DNA and protein were detected in the bone marrow of 5 patients studied prospectively and in 1 of 40 patients studied retrospectively. As estimated by in-situ hybridization, about 3% to 5% of marrow cells were infected with virus in those patients who had not received acyclovir. In contrast, Epstein-Barr virus DNA was not detected in peripheral blood DNA of these patients, nor were Epstein-Barr virus proteins or DNA found in the bone marrow of normal donors, patients with other hematologic diseases, or in 1 patient with acute infectious mononucleosis. Analysis of DNA fragments by hybridization with Epstein-Barr virus probes showed a pattern dissimilar to the type of Epstein-Barr virus usually associated with infectious mononucleosis.

Conclusions: Aplastic anemia may be associated with Epstein-Barr virus more commonly than suspected by history. Localization of the virus in the bone marrow supports a causative role for Epstein-Barr virus in bone marrow failure.





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