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Journal of Virology, May 1999, p. 4019-4028, Vol. 73, No. 5
0022-538X/99/$04.00+0

Human Herpesvirus 6 Infects Dendritic Cells and Suppresses Human Immunodeficiency Virus Type 1 Replication in Coinfected Cultures

Hideo Asada,1 Vera Klaus-Kovtun,1 Hana Golding,2 Stephen I. Katz,1 and Andrew Blauvelt1,*

Dermatology Branch, National Cancer Institute,1 and Division of Viral Products, Center for Biologics Evaluation and Research, Food and Drug Administration,2 Bethesda, Maryland 20892

Received 23 October 1998/Accepted 1 February 1999

Human herpesvirus 6 (HHV-6) has been implicated as a cofactor in the progressive loss of CD4+ T cells observed in AIDS patients. Because dendritic cells (DC) play an important role in the immunopathogenesis of human immunodeficiency virus (HIV) disease, we studied the infection of DC by HHV-6 and coinfection of DC by HHV-6 and HIV. Purified immature DC (derived from adherent peripheral blood mononuclear cells in the presence of granulocyte-macrophage colony-stimulating factor and interleukin-4) could be infected with HHV-6, as determined by PCR analyses, intracellular monoclonal antibody staining, and presence of virus in culture supernatants. However, HHV-6-infected DC demonstrated neither cytopathic changes nor functional defects. Interestingly, HHV-6 markedly suppressed HIV replication and syncytium formation in coinfected DC cultures. This HHV-6-mediated anti-HIV effect was DC specific, occurred when HHV-6 was added either before or after HIV, and was not due to decreased surface expression or function of CD4, CXCR4, or CCR5. Conversely, HIV had no demonstrable effect on HHV-6 replication. These findings suggest that HHV-6 may protect DC from HIV-induced cytopathicity in AIDS patients. We also demonstrate that interactions between HIV and herpesviruses are complex and that the observable outcome of dual infection is dependent on the target cell type.


* Corresponding author. Mailing address: Dermatology Branch, National Cancer Institute, Building 10/Room 12N238, 10 Center Dr. MSC 1908, Bethesda, MD 20892-1908. Phone: (301) 402-4167. Fax: (301) 402-1439. E-mail: Andrew_Blauvelt{at}nih.gov.


Journal of Virology, May 1999, p. 4019-4028, Vol. 73, No. 5
0022-538X/99/$04.00+0



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