HUMAN HERPESVIRUS-6 INDUCES INTERLEUKIN-1-BETA AND TUMOR-NECROSIS-FACTOR-ALPHA, BUT NOT INTERLEUKIN-6, IN PERIPHERAL-BLOOD MONONUCLEAR CELL-CULTURES

The human herpesvirus 6 (HHV-6) is known to interact intimately with cells of the immune system. Here we report that HHV-6 is a potent inducer of interleukin-1-beta (IL-1-beta) and tumor necrosis factor alpha (TNF-alpha) in cultures of peripheral blood mononuclear cells. In contradistinction, HHV-6 has no effect on IL-6 synthesis. Maximal IL-1-beta and TNF-alpha-gene transcription, as detected by polymerase chain reaction amplification analysis, is observed at 12 and 6 h postinfection, respectively. Release of IL-1-beta and TNF-alpha-into the culture supernatants peaked at 24 h and gradually decreased with time. Heat-inactivated virus was unable to stimulate IL-1-beta and TNF-alpha-syntheses, whereas UV-irradiated virus retained the full monokine-inducing potential of the native particle. Preincubation of viral preparation with neutralizing anti-HHV-6 antibody resulted in the abrogation of this cytokine-inducing effect, whereas treatment of cells with phosphonoacetic acid (an inhibitor of viral DNA polymerase activity) had no effect on the ability of the virus to stimulate monokine release. These results indicate that HHV-6 can exert a strong immunomodulatory effect by stimulating the cells of myeloid lineage to produce these cytokines.