Implication of macrophage inflammatory protein-1alpha in the inhibition of human haematopoietic progenitor growth by dengue virus.

Abstract

The mechanisms were investigated of haematopoietic progenitor growth inhibition, 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 with 29-56DSS compared with a prototype strain of dengue 3 (H-87) which had no inhibitory effect. An inhibitory effect was also observed when cell-free and heat-inactivated supernatants from 29-56DSS cultures, but not from H-87 cultures, were added to cultures of normal CBMNC, suggesting an indirect mechanism via the release of soluble suppressive factor(s). Macrophage inflammatory protein-1alpha (MIP-1alpha) was detected at a significantly higher level in 29-56DSS cultures than in controls. Blocking experiments with anti-MIP-1alpha antibody demonstrated that the inhibitory effect was related at least partly to high MIP-1alpha levels. To our knowledge, this is the first report suggesting an indirect effect of dengue infection on haematopoiesis mediated by a suppressive cytokine.