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Human herpesvirus 6 (HHV-6)-associated dysfunction of blood monocytes
1Department of Pathology, Medical College of Wisconsin, Milwaukee 53226.
Abstract:
HHV-6 is a recently described member of the herpesvirus family. HHV-6-associated marrow failure and interstitial pneumonitis where macrophages are the primary infected cell type have been described in marrow transplant patients (Carrigan, 1991; Drobyski et al., 1993). In recent studies 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 Carrigan, 1993). Additional experiments using HHV-6GS to characterize the effects of the virus on peripheral blood monocytes showed that the respiratory burst capacity of these cells as determined by luminol-enhanced chemiluminescence using phorbol myristate acetate as a trigger was decreased by 83% +/- 13% in a series of 5 experiments. The decreased respiratory burst was evident as early as 15 min after exposure to virus. Experiments in which cells were separated on a fluorescence activated cell sorter prior to respiratory burst assay showed that the response was mediated solely by peripheral blood monocytes. The respiratory burst response of virus-exposed cells to opsonized zymosan was not affected, indicating that the virus may selectively interfere with the protein 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 suggest that HHV-6 infection may be associated with a defect in one of the major monocyte activation pathways, and this could be of importance with respect to persistent infection by HHV-6 in immune compromised patients.
Insights
Human herpesvirus 6 (HHV-6) infection significantly impairs monocyte function, decreasing their respiratory burst capacity. This viral effect on immune cells may contribute to persistent HHV-6 infections in immunocompromised individuals.
Area of Science:
- Virology
- Immunology
- Cell Biology
Background:
- Human herpesvirus 6 (HHV-6) is a member of the herpesvirus family.
- HHV-6 has been linked to marrow failure and interstitial pneumonitis in transplant patients, with macrophages as the primary infected cells.
- Previous studies indicated HHV-6 suppresses macrophage outgrowth from human marrow.
Purpose of the Study:
- To investigate the effects of HHV-6 on the function of peripheral blood monocytes.
- To determine the mechanism by which HHV-6 impacts monocyte activation pathways.
Main Methods:
- Exposure of normal human marrow and peripheral blood monocytes to HHV-6 strains (Type A and Type B).
- Assay of monocyte respiratory burst capacity using luminol-enhanced chemiluminescence with phorbol myristate acetate and opsonized zymosan.
- Cell sorting (fluorescence-activated cell sorter) to isolate monocyte populations.
- Ultracentrifugation of viral stock to identify the suppressive factor.
Main Results:
- HHV-6 exposure suppressed growth factor-induced macrophage outgrowth by over 90%.
- Respiratory burst capacity of peripheral blood monocytes decreased by 83% +/- 13% within 15 minutes of HHV-6 exposure.
- The suppressive effect was mediated solely by monocytes and did not affect responses to opsonized zymosan, suggesting interference with the protein kinase C pathway.
- The suppressive factor was found in the supernatant fraction, not associated with infectious virus particles.
Conclusions:
- HHV-6 infection can induce a defect in a major monocyte activation pathway.
- This impairment of monocyte function may play a role in persistent HHV-6 infections, particularly in immunocompromised patients.
- Further research is needed to elucidate the precise mechanisms and clinical implications of HHV-6-induced monocyte dysfunction.