Increased intracellular accumulation of macrophage inflammatory protein 1beta and its decreased secretion correlate with advanced HIV disease

Considering that the chemokine macrophage inflammatory protein 1beta (MIP1beta) may serve as a competitive inhibitor for HIV entry, the objective of this study was to compare intracellular and extracellular levels of MIP1beta, in untreated HIV-infected individuals. HIV patients and healthy controls were tested by two-color flow cytometry for intracellular MIP1beta, in freshly explanted CD4 and CD8 lymphocytes, and in monocytes. Sera and plasma collected on the same day were tested, respectively, by enzyme-linked immunosorbent assay (ELISA) for MIP1beta concentration and for number of HIV-RNA copies, using nucleic acid sequence-based amplification procedure (NASBA) methodology. Results demonstrate that a high intracellular level of MIP1beta appears to be linked to a deterioration in the immune status of HIV patients (i.e., low CD4 counts) and to a high viral load. Moreover, an inverse relationship exists between the intracellular and the "secreted" form of MIP1beta, thus leading to the hypothesis that the regulation of cellular accumulation and secretion of MIP1beta and of other chemokines may be disrupted during AIDS development.