Human cytomegalovirus-associated immunosuppression is mediated through interferon-alpha.
Human cytomegalovirus (HCMV) infections are commonly associated with a generalized immunologic hyporesponsiveness. The present study was designed to evaluate the potential mechanisms of HCMV-associated immunosuppression. In our initial experiments, monocytes in peripheral blood mononuclear cells (PBMCs) exposed to cell-free HCMV appeared morphologically less differentiated than monocytes in PBMCs exposed to a mock preparation. These morphologic changes were closely correlated with a decrease in monocyte oxidative activity and occurred under noncytopathic conditions. HCMV-associated suppression of monocyte differentiation did not require virus replication, occurred in PBMCs from either HCMV seropositive or seronegative donors, and required HCMV interaction with the nonadherent cells. An HCMV-induced soluble factor was found to not only reproduce the identical changes in purified monocytes but to inhibit the phagocytic activity of these cells. Additionally, the HCMV-induced factor accounted for a generalized defect in the ability of PBMCs to proliferate in response to mitogens and recall antigens. In subsequent experiments, interferon-alpha (IFN-alpha) was identified as the soluble factor involved in these immunosuppressive effects. Thus, PBMCs, when exposed to HCMV, produce a soluble factor, identified as IFN-alpha, that appears to be an important mediator of immunosuppression associated with HCMV infection.
Noraz
N
N
Department of Pediatrics, University of California, San Diego, La Jolla 92093-0672, USA.
Lathey
J L
JL
Spector
S A
SA
D002454:Cell Differentiation; D002478:Cells, Cultured; D017077:Culture Media, Conditioned / Q000494:pharmacology; D003587:Cytomegalovirus / Q000502:physiology*; D003586:Cytomegalovirus Infections / Q000276:immunology; D006801:Humans; D007153:Immunologic Deficiency Syndromes / Q000821:virology*; D007156:Immunologic Memory; D016898:Interferon-alpha / Q000096:biosynthesis / Q000502:physiology*; D008213:Lymphocyte Activation; D009000:Monocytes / Q000276:immunology / Q000378:metabolism / Q000821:virology*; D010587:Phagocytosis
D017077:Culture Media, Conditioned; D016898:Interferon-alpha