BACKGROUND. Human herpesvirus 6 (HHV-6) is a recently discovered virus that, on the basis of serologic evidence, appears to infect most children by the age of three years. However, the clinical manifestations of primary HHV-6 infection have not been well defined. METHODS. We studied consecutive children two years old or younger who presented to an emergency ward with febrile illnesses. Our evaluation included the isolation of HHV-6 from peripheral-blood mononuclear cells, an immunofluorescent-antibody assay, the detection of HHV-6 by the polymerase chain reaction (PCR), and restriction-endonuclease-fragment profiles of HHV-6 isolates. RESULTS. HHV-6 was isolated from 34 of 243 acutely ill children (14 percent). The children with viremia had irritability, high temperatures (mean, 39.7 degrees C), and inflammation of tympanic membranes (in 21), but few other localizing signs. Two children were hospitalized, but all 34 recovered after an average of four days of fever. The rash characteristic of roseola, which has been associated with HHV-6 infection, was noted in only three children. In 29 children (85 percent), serum samples obtained during convalescence had at least a fourfold increase in IgG antibody titers; 4 infants less than three months old who presumably had maternal antibody did not have this increase. HHV-6 was isolated from blood obtained during convalescence in only one child, but in two thirds of the children the virus could be detected by PCR. The isolates had genomic heterogeneity, indicating the presence of multiple strains. CONCLUSIONS. Primary infection with HHV-6 is a major cause of acute febrile illness in young children. Such infection is associated with varied clinical manifestations, viremia, and the frequent persistence of the viral genome in mononuclear cells.
Source Information
Department of Pediatrics, University of Rochester School of Medicine, N.Y. 14642-8689.
This article has been cited by other articles:
Zhen, Z., Bradel-Tretheway, B., Sumagin, S., Bidlack, J. M., Dewhurst, S.
(2005). The Human Herpesvirus 6 G Protein-Coupled Receptor Homolog U51 Positively Regulates Virus Replication and Enhances Cell-Cell Fusion In Vitro. J. Virol.
79: 11914-11924
[Abstract][Full Text]
Zerr, D. M., Meier, A. S., Selke, S. S., Frenkel, L. M., Huang, M.-L., Wald, A., Rhoads, M. P., Nguy, L., Bornemann, R., Morrow, R. A., Corey, L.
(2005). A Population-Based Study of Primary Human Herpesvirus 6 Infection. NEJM
352: 768-776
[Abstract][Full Text]
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]
Wong, G. A. E., Shear, N. H.
(2004). Is a Drug Alone Sufficient to Cause the Drug Hypersensitivity Syndrome?. Arch Dermatol
140: 226-230
[Full Text]
Harada, S., Kamata, Y., Ishii, Y., Eda, H., Kitamura, R., Obayashi, M., Ito, S., Ban, F., Kuranari, J., Nakajima, H., Kuze, T., Hayashi, M., Okabe, N., Senpuku, H., Miyasaka, N., Nakamura, Y., Kanegane, H., Yanagi, K.
(2004). Maintenance of Serum Immunoglobulin G Antibodies to Epstein-Barr Virus (EBV) Nuclear Antigen 2 in Healthy Individuals from Different Age Groups in a Japanese Population with a High Childhood Incidence of Asymptomatic Primary EBV Infection. CVI
11: 123-130
[Abstract][Full Text]
Sitki-Green, D., Covington, M., Raab-Traub, N.
(2003). Compartmentalization and Transmission of Multiple Epstein-Barr Virus Strains in Asymptomatic Carriers. J. Virol.
77: 1840-1847
[Abstract][Full Text]
Dockrell, D.H.
(2003). Human herpesvirus 6: molecular biology and clinical features. J Med Microbiol
52: 5-18
[Abstract][Full Text]
Andreoni, M., Sarmati, L., Nicastri, E., El Sawaf, G., El Zalabani, M., Uccella, I., Bugarini, R., Parisi, S. G., Rezza, G.
(2002). Primary Human Herpesvirus 8 Infection in Immunocompetent Children. JAMA
287: 1295-1300
[Abstract][Full Text]
Skrincosky, D., Hocknell, P., Whetter, L., Secchiero, P., Chandran, B., Dewhurst, S.
(2000). Identification and Analysis of a Novel Heparin-Binding Glycoprotein Encoded by Human Herpesvirus 7. J. Virol.
74: 4530-4540
[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]
Ansari, A., Emery, V. C.
(1999). The U69 Gene of Human Herpesvirus 6 Encodes a Protein Kinase Which Can Confer Ganciclovir Sensitivity to Baculoviruses. J. Virol.
73: 3284-3291
[Abstract][Full Text]
Drago, F., Rebora, A.
(1999). The New Herpesviruses: Emerging Pathogens of Dermatological Interest. Arch Dermatol
135: 71-75
[Abstract][Full Text]
Luppi, M., Barozzi, P., Garber, R., Maiorana, A., Bonacorsi, G., Artusi, T., Trovato, R., Marasca, R., Torelli, G.
(1998). Expression of Human Herpesvirus-6 Antigens in Benign and Malignant Lymphoproliferative Diseases. Am. J. Pathol.
153: 815-823
[Abstract][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]
Hukin, J., Farrell, K., MacWilliam, L. M, Colbourne, M., Waida, E., Tan, R., Mroz, L., Thomas, E.
(1998). Case-Control Study of Primary Human Herpesvirus 6 Infection in Children With Febrile Seizures. Pediatrics
101
: e3-e3
[Abstract][Full Text]
Osiowy, C, Prud'homme, I, Monette, M, Zou, S
(1998). Detection of human herpesvirus 6 DNA in serum by a microplate PCR- hybridization assay [In Process Citation]. J. Clin. Microbiol.
36: 68-72
[Abstract][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]
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]
Cone, R. W., Hackman, R. C., Huang, M.-L. W., Bowden, R. A., Meyers, J. D., Metcalf, M., Zeh, J., Ashley, R., Corey, L.
(1993). Human Herpesvirus 6 in Lung Tissue from Patients with Pneumonitis after Bone Marrow Transplantation. NEJM
329: 156-161
[Abstract][Full Text]
Akashi, K., Eizuru, Y., Sumiyoshi, Y., Minematsu, T., Hara, S., Harada, M., Kikuchi, M., Niho, Y., Minamishima, Y.
(1993). Severe Infectious Mononucleosis-like Syndrome and Primary Human Herpesvirus 6 Infection in an Adult. NEJM
329: 168-171
[Full Text]
Agut, H.
(1993). Puzzles Concerning the Pathogenicity of Human Herpesvirus 6. NEJM
329: 203-204
[Full Text]
(1992). HERPESVIRUS-6: A FREQUENT CAUSE OF ACUTE FEBRILE ILLNESS IN CHILDREN. JWatch General
1992: 3-3
[Full Text]