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Original Article
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Volume 329:156-161 July 15, 1993 Number 3
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Human Herpesvirus 6 in Lung Tissue from Patients with Pneumonitis after Bone Marrow Transplantation
Richard W. Cone, Robert C. Hackman, Meei-Li W. Huang, Raleigh A. Bowden, Joel D. Meyers, Mark Metcalf, Judith Zeh, Rhoda Ashley, and Lawrence Corey

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ABSTRACT

Background Human herpesvirus 6 (HHV-6) is a recently described herpesvirus that is epidemiologically and biologically similar to cytomegalovirus. It is the cause of exanthem subitum (roseola) in children.

Methods To evaluate the possible role of HHV-6 infection in pneumonitis in immunocompromised patients, we used quantitative HHV-6 polymerase chain reactions to study lung-biopsy specimens from 15 patients with pneumonitis after bone marrow transplantation and lung tissue from 15 immunocompetent subjects without pneumonitis and 6 fetuses.

Results HHV-6 DNA was detected in lung tissue from all 15 patients, from 14 seropositive control subjects, and from none of the 7 seronegative control subjects. Six patients had levels of HHV-6 DNA in lung tissue that were 10 to 500 times higher than those in any of the other patients or control subjects. Increased levels of HHV-6 DNA correlated with a decreased risk of death from pneumonitis (P = 0.015), an increased severity of graft-versus-host disease (P = 0.023), and the presence of idiopathic pneumonitis (P = 0.037). Levels of HHV-6 DNA correlated directly with the changes in HHV-6 antibody titers in the interval between the pretransplantation period and the open-lung biopsy (P = 0.002). Low levels of HHV-6 antibody at the time of the open-lung biopsy were also associated with the diagnosis of idiopathic pneumonitis (P = 0.002).

Conclusions The concentrations of HHV-6 genome in lung tissue and their relation to changes in serologic titers support an association between HHV-6 infection and idiopathic pneumonitis in immunocompromised hosts.


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From the Departments of Laboratory Medicine (R.W.C., M.-L.W.H., M.M., R.A., L.C.), Medicine (L.C.), Pathology (R.C.H.), Pediatrics (R.A.B.), and Statistics (J.Z.), University of Washington, and the Departments of Pathology (R.C.H.) and Infectious Diseases (R.A.B., J.D.M.), Fred Hutchinson Cancer Research Center, both in Seattle. A portion of this work was presented in abstract form at the 14th International Herpesvirus Workshop, Nyborg Strand, Denmark, August 20-26, 1989.Dr. Joel D. Meyers is deceased.

Address reprint requests to Dr. Cone at Children's Hospital and Medical Center, CH-82, 4800 Sand Point Way NE, Seattle, WA 98105.

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