Human herpesvirus 6 infects dendritic cells and suppresses human immunodeficiency virus type 1 replication in coinfected cultures

Human herpesvirus 6 (HHV-6) has been implicated as a cofactor in the progre ssive loss of CD4(+) T cells observed in AIDS patients. Because dendritic c ells (DC) play an important role in the immunopathogenesis of human immunod eficiency 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 adhe rent peripheral blood mononuclear cells in the presence of granulocyte-macr ophage colony-stimulating factor and interleukin-4) could be infected with HHV-6, as determined by PCR analyses, intracellular monoclonal antibody sta ining, and presence of virus in culture supernatants. However, HHV-6-infect ed DC demonstrated neither cytopathic changes nor functional defects. Inter estingly, HHV-6 markedly suppressed HIV replication and syncytium formation in coinfected DC cultures. This HHV-6-mediated anti-HIV effect was DC spec ific, 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. Co nversely, HIV had no demonstrable effect on HHV-6 replication, These findin gs suggest that HHV-6 may protect DC from HIV-induced cytopathicity in AIDS patients. We also demonstrate that interactions between HIV and herpesviru ses are complex and that the observable outcome of dual infection is depend ent on the target cell type.