IMPLICATION OF MACROPHAGE INFLAMMATORY PROTEIN-1-ALPHA IN THE INHIBITION OF HUMAN HEMATOPOIETIC PROGENITOR GROWTH BY DENGUE VIRUS

The mechanisms were investigated of haematopoietic progenitor growth i nhibition, observed after in vitro infection of cord blood mononuclear cells (CBMNC) by a clinical isolate of dengue 3 (29-56DSS). The level of virus replication was not different when CBMNC were inoculated wit h 29-56DSS compared with a prototype strain of dengue 3 (H-87) which h ad no inhibitory effect. An inhibitory effect was also observed when c ell-free and heat-inactivated supernatants from 29-56DSS cultures, but not from H-87 cultures, were added to cultures of normal CBMNC, sugge sting an indirect mechanism via the release of soluble suppressive fac tor(s). Macrophage inflammatory protein-1 alpha (MIP-1 alpha) was dete cted at a significantly higher level in 29-56DSS cultures than in cont rols. Blocking experiments with anti-MIP-1 alpha antibody demonstrated that the inhibitory effect was related at least partly to high MIP-1 alpha levels. To our knowledge, this is the first report suggesting an indirect effect of dengue infection on haematopoiesis mediated by a s uppressive cytokine.