Background Human herpesvirus 6 (HHV-6) is a recently describedherpesvirus that is epidemiologically and biologically similarto cytomegalovirus. It is the cause of exanthem subitum (roseola)in children.
Methods To evaluate the possible role of HHV-6 infection inpneumonitis in immunocompromised patients, we used quantitativeHHV-6 polymerase chain reactions to study lung-biopsy specimensfrom 15 patients with pneumonitis after bone marrow transplantationand lung tissue from 15 immunocompetent subjects without pneumonitisand 6 fetuses.
Results HHV-6 DNA was detected in lung tissue from all 15 patients,from 14 seropositive control subjects, and from none of the7 seronegative control subjects. Six patients had levels ofHHV-6 DNA in lung tissue that were 10 to 500 times higher thanthose in any of the other patients or control subjects. Increasedlevels of HHV-6 DNA correlated with a decreased risk of deathfrom pneumonitis (P = 0.015), an increased severity of graft-versus-hostdisease (P = 0.023), and the presence of idiopathic pneumonitis(P = 0.037). Levels of HHV-6 DNA correlated directly with thechanges in HHV-6 antibody titers in the interval between thepretransplantation period and the open-lung biopsy (P = 0.002).Low levels of HHV-6 antibody at the time of the open-lung biopsywere also associated with the diagnosis of idiopathic pneumonitis(P = 0.002).
Conclusions The concentrations of HHV-6 genome in lung tissueand their relation to changes in serologic titers support anassociation between HHV-6 infection and idiopathic pneumonitisin immunocompromised hosts.
Source Information
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.
De Bolle, L., Naesens, L., De Clercq, E.
(2005). Update on Human Herpesvirus 6 Biology, Clinical Features, and Therapy. Clin. Microbiol. Rev.
18: 217-245
[Abstract][Full Text]
Vuorinen, T., Kotilainen, P., Lautenschlager, I., Kujari, H., Krogerus, L., Oksi, J.
(2004). Interstitial Pneumonitis and Coinfection of Human Herpesvirus 6 and Pneumocystis carinii in a Patient with Hypogammaglobulinemia. J. Clin. Microbiol.
42: 5415-5418
[Abstract][Full Text]
Kotloff, R. M., Ahya, V. N., Crawford, S. W.
(2004). Pulmonary Complications of Solid Organ and Hematopoietic Stem Cell Transplantation. Am. J. Respir. Crit. Care Med.
170: 22-48
[Abstract][Full Text]
Ihira, M., Yoshikawa, T., Enomoto, Y., Akimoto, S., Ohashi, M., Suga, S., Nishimura, N., Ozaki, T., Nishiyama, Y., Notomi, T., Ohta, Y., Asano, Y.
(2004). Rapid Diagnosis of Human Herpesvirus 6 Infection by a Novel DNA Amplification Method, Loop-Mediated Isothermal Amplification. J. Clin. Microbiol.
42: 140-145
[Abstract][Full Text]
Dockrell, D.H.
(2003). Human herpesvirus 6: molecular biology and clinical features. J Med Microbiol
52: 5-18
[Abstract][Full Text]
Yoshikawa, T., Black, J. B., Ihira, M., Suzuki, K., Suga, S., Iida, K., Saito, Y., Asonuma, K., Tanaka, K., Asano, Y.
(2001). Comparison of Specific Serological Assays for Diagnosing Human Herpesvirus 6 Infection after Liver Transplantation. CVI
8: 170-173
[Abstract][Full Text]
Zou, P., Isegawa, Y., Nakano, K., Haque, M., Horiguchi, Y., Yamanishi, K.
(1999). Human Herpesvirus 6 Open Reading Frame U83 Encodes a Functional Chemokine. J. Virol.
73: 5926-5933
[Abstract][Full Text]
Asada, H., Klaus-Kovtun, V., Golding, H., Katz, S. I., Blauvelt, A.
(1999). Human Herpesvirus 6 Infects Dendritic Cells and Suppresses Human Immunodeficiency Virus Type 1 Replication in Coinfected Cultures. J. Virol.
73: 4019-4028
[Abstract][Full Text]
Drago, F., Rebora, A.
(1999). The New Herpesviruses: Emerging Pathogens of Dermatological Interest. Arch Dermatol
135: 71-75
[Abstract][Full Text]
Rotola, A., Ravaioli, T., Gonelli, A., Dewhurst, S., Cassai, E., Di Luca, D.
(1998). U94 of human herpesvirus 6 is expressed in latently infected peripheral blood mononuclear cells and blocks viral gene expression in transformed lymphocytes in culture. Proc. Natl. Acad. Sci. USA
95: 13911-13916
[Abstract][Full Text]
Le Cleach, L., Fillet, A. M., Agut, H., Chosidow, O.
(1998). Human Herpesviruses 6 and 7: New Roles Yet to Be Discovered?. Arch Dermatol
134: 1155-1157
[Full Text]
Mirandola, P., Menegazzi, P., Merighi, S., Ravaioli, T., Cassai, E., Di Luca, D.
(1998). Temporal Mapping of Transcripts in Herpesvirus 6 Variants. J. Virol.
72: 3837-3844
[Abstract][Full Text]
Deng, H., Dewhurst, S.
(1998). Functional Identification and Analysis of cis-Acting Sequences Which Mediate Genome Cleavage and Packaging in Human Herpesvirus 6. J. Virol.
72: 320-329
[Abstract][Full Text]
Stone, R. M., Mark, E. J., Ferry, J. A.
(1997). Case 31-1997- A 67-Year-Old Renal-Transplant-Recipient with Anemia, Leukopenia, and Pulmonary Lesions. NEJM
337: 1065-1074
[Full Text]
KOTSIMBOS, A.T. C., SINICKAS, V., GLARE, E. M., ESMORE, D. S., SNELL, G. I., WALTERS, E. H., WILLIAMS, T. J.
(1997). Quantitative Detection of Human Cytomegalovirus DNA in Lung Transplant Recipients. Am. J. Respir. Crit. Care Med.
156: 1241-1246
[Abstract][Full Text]
SATTLER, F., NICHOLS, L., HIRANO, L., HITI, A., HOFMAN, F., HUGHLETT, C., ZENG, L., BOYLEN, C. T., KOSS, M.
(1997). Nonspecific Interstitial Pneumonitis Mimicking Pneumocystis carinii Pneumonia. Am. J. Respir. Crit. Care Med.
156: 912-917
[Abstract][Full Text]
Elias, A. D., Mark, E. J.
(1997). Case 25-1997- A 60-Year-Old Man with Pulmonary Infiltrates after a Bone Marrow Transplantation. NEJM
337: 480-489
[Full Text]
Bandobashi, K., Daibata, M., Kamioka, M., Tanaka, Y., Kubonishi, I., Taguchi, H., Ohtsuki, Y., Miyoshi, I.
(1997). Human Herpesvirus 6 (HHV-6)-Positive Burkitt's Lymphoma: Establishment of a Novel Cell Line Infected With HHV-6. Blood
90: 1200-1207
[Abstract][Full Text]
Luppi, M., Torelli, G.
(1996). Human Herpesvirus 8 and Interstitial Pneumonitis in an HIV-Negative Patient. NEJM
335: 351-352
[Full Text]
Hall, C. B., Long, C. E., Schnabel, K. C., Caserta, M. T., McIntyre, K. M., Costanzo, M. A., Knott, A., Dewhurst, S., Insel, R. A., Epstein, L. G.
(1994). Human Herpesvirus-6 Infection in Children -- A Prospective Study of Complications and Reactivation. NEJM
331: 432-438
[Abstract][Full Text]
Drobyski, W. R., Knox, K. K., Majewski, D., Carrigan, D. R.
(1994). Fatal Encephalitis Due to Variant B Human Herpesvirus-6 Infection in a Bone Marrow-Transplant Recipient. NEJM
330: 1356-1360
[Full Text]
Morris, D. J., Appleton, A. L., Sviland, L., Schmidt, C.A., Wilborn, F.F., Siegert, W., Cone, R., Corey, L., Hackman, R., Akashi, K., Eizuru, Y., Sumiyoshi, Y.
(1993). Primary Human Herpesvirus 6 Infection in an Adult. NEJM
329: 1817-1819
[Full Text]
(1993). New Disease Associations for Herpes-6. Journal Watch Dermatology
1993: 13-13
[Full Text]
(1993). NEW DISEASE ASSOCIATIONS FOR HERPES-6. JWatch General
1993: 4-4
[Full Text]
Agut, H.
(1993). Puzzles Concerning the Pathogenicity of Human Herpesvirus 6. NEJM
329: 203-204
[Full Text]