Extracellular high mobility group box-1 inhibits R5 and X4 HIV-1 strains replication in mononuclear phagocytes without induction of chemokines and cytokines
- 13 March 2009
- journal article
- Published by Ovid Technologies (Wolters Kluwer Health) in AIDS
- Vol. 23 (5), 567-577
- https://doi.org/10.1097/qad.0b013e328325a47e
Abstract
High mobility group box-1 (HMGB1) is a nuclear chromatin protein. Furthermore, it induces chemotaxis and inflammation once released in the extracellular milieu, and it has been reported to upregulate, but also to inhibit HIV-1 replication in different cell types. We here investigated the potential role of extracellular HMGB1 in both R5 and X4 HIV-1 replication in primary human monocyte-derived macrophages (MDM) and U937 promonocytic cells, respectively.MDM or U937 cells were infected with R5 and X4 HIV-1 strains, respectively, in the presence or absence of endotoxin-free recombinant (r) HMGB1 or necrotic cell supernatants either containing or depleted of endogenous HMGB1.HIV replication was measured by means of virion-associated reverse transcriptase activity in culture supernatants and cell-associated viral protein expression. Cytokine and chemokine production were measured by enzyme-linked immunosorbent assay; cell surface expression of CD4, CC chemokine receptor 5, receptor for advanced glycation end-products, Toll-like receptor-2 and Toll-like receptor-4 were analyzed by flow cytometry.Both rHMGB1 and necrotic cell supernatant-associated HMGB1 inhibited replication of R5 HIV-1 in MDM. Surprisingly enough, no upregulation of CC chemokine receptor 5-binding chemokines or of other chemokines and cytokines was observed in rHMGB1-stimulated MDM. HMGB1 also induced chemotaxis and strongly inhibited the replication of X4 HIV-1 in the 'Minus' subset of U937 cell clones expressing high levels of putative HMGB1 receptors (receptor for advanced glycation end-products, Toll-like receptors 2 and 4).Extracellular HMGB1 is a potent inhibitor of both R5 and X4 HIV-1 replication in mononuclear phagocytic cells without inducing the release of HIV-Modulatory chemokines or cytokines.Keywords
This publication has 62 references indexed in Scilit:
- HMGB1-Dependent Triggering of HIV-1 Replication and Persistence in Dendritic Cells as a Consequence of NK-DC Cross-TalkPLOS ONE, 2008
- A novel role for HMGB1 in TLR9-mediated inflammatory responses to CpG-DNABlood, 2007
- Inhibition of HIV replication by the plasminogen activator is dependent on vitronectin-mediated cell adhesionJournal of Leukocyte Biology, 2007
- The evolution of High Mobility Group Box (HMGB) chromatin proteins in multicellular animalsGene, 2007
- Microbial translocation is a cause of systemic immune activation in chronic HIV infectionNature Medicine, 2006
- Pathogenic role of HMGB1 in SARS?Medical Hypotheses, 2004
- Consequences of Cell DeathThe Journal of Experimental Medicine, 2000
- Increased replication of T-cell-tropic HIV strains and CXC-chemokine receptor-4 induction in T cells treated with macrophage inflammatory protein (MIP)-1α, MIP-1β and RANTES β-chemokinesAIDS, 1998
- The β-Chemokine Receptors CCR3 and CCR5 Facilitate Infection by Primary HIV-1 IsolatesCell, 1996
- A family of serine proteases expressed exclusively in myelo-monocytic cells specifically processes the nuclear factor-kappa B subunit p65 in vitro and may impair human immunodeficiency virus replication in these cells.The Journal of Experimental Medicine, 1994