Host hindrance to HIV-1 replication in monocytes and macrophages

Monocytes and macrophages are targets of HIV-1 infection and play critical roles in multiple aspects of viral pathogenesis. HIV-1 can replicate in blood monocytes, although only a minor proportion of circulating monocytes harbor viral DNA. Resident macrophages in tissues can be infected and function as viral reservoirs. However, their susceptibility to infection, and their capacity to actively replicate the virus, varies greatly depending on the tissue localization and cytokine environment. The susceptibility of monocytes to HIV-1 infection in vitro depends on their differentiation status. Monocytes are refractory to infection and become permissive upon differentiation into macrophages. In addition, the capacity of monocyte-derived macrophages to sustain viral replication varies between individuals. Host determinants regulate HIV-1 replication in monocytes and macrophages, limiting several steps of the viral life-cycle, from viral entry to virus release. Some host factors responsible for HIV-1 restriction are shared with T lymphocytes, but several anti-viral mechanisms are specific to either monocytes or macrophages. Whilst a number of these mechanisms have been identified in monocytes or in monocyte-derived macrophages in vitro, some of them have also been implicated in the regulation of HIV-1 infection in vivo, in particular in the brain and the lung where macrophages are the main cell type infected by HIV-1. This review focuses on cellular factors that have been reported to interfere with HIV-1 infection in monocytes and macrophages, and examines the evidences supporting their role in vivo, highlighting unique aspects of HIV-1 restriction in these two cell types

PMA-induced down-regulation of the receptor for alpha2-macroglobulin in human U937 cells.

AbstractTranscription and expression of the urokinase (uPA) receptor (uPAR) are strongly stimulated by PMA. As for uPAR, the expression of α2-MR is regulated by PMA in U937 cells. Ligand blotting experiments with the 39 kDa receptor-associated protein RAP, a ligand for α2-MR, indicated that α2-MR levels first increased and then decreased after PMA treatment. FACscan as well as immunoblotting analysis with α2-MR-specific antibodies showed an identical trend: α2-MR levels increased within the first day of treatment with PMA, decreased at later times, and totally disappeared by three days of treatment. The effect of PMA was not due to transcriptional down-regulation, as the α2-MR mRNA level did not decrease at later times. Sensitivity of U937 cells to uPA-saporin, a toxin conjugate that reguires binding to WAR for killing activity, was also markedly decreased. These results suggest that uPAR-mediated endocytosis depends on α2-MR expression