HUMAN HERPESVIRUS-6 (HHV-6)-ASSOCIATED DYSFUNCTION OF BLOOD MONOCYTES

HHV-6 is a recently described member of the herpesvirus family. HHV-6- associated marrow failure and interstitial pneumonitis where macrophag es are the primary infected cell type have been described in marrow tr ansplant patients (Carrigan, 1991; Drobyski et al., 1993). In recent s tudies we have shown that exposure of normal human marrow to HHV-6GS ( a type A strain) or several type B strains resulted in suppression of growth factor induced outgrowth of macrophages by > 90% (Burd and Carr igan, 1993). Additional experiments using HHV-6GS to characterize the effects of the virus on peripheral blood monocytes showed that the res piratory burst capacity of these cells as determined by luminol-enhanc ed chemiluminescence using phorbol myristate acetate as a trigger was decreased by 83% +/- 13% in a series of 5 experiments. The decreased r espiratory burst was evident as early as 15 min after exposure to viru s. Experiments in which cells were separated on a fluorescence activat ed cell sorter prior to respiratory burst assay showed that the respon se was mediated solely by peripheral blood monocytes. The respiratory burst response of virus-exposed cells to opsonized zymosan was not aff ected, indicating that the virus may selectively interfere with the pr otein kinase C pathway of cellular activation. Ultracentrifugation of stock material to remove infectious virus showed that the suppressive factor was associated with the supernatant fraction. These findings su ggest that HHV-6 infection may be associated with a defect in one of t he major monocyte activation pathways. and this could be of importance with respect to persistent infection by HHV-6 in immune compromised p atients.