Role of the β-Chemokine Receptors CCR3 and CCR5 in Human Immunodeficiency Virus Type 1 Infection of Monocytes and Microglia

Abstract

Human immunodeficiency virus type 1 (HIV-1) infection in mononuclear phagocyte lineage cells (monocytes, macrophages, and microglia) is a critical component in the pathogenesis of viral infection. Viral replication in macrophages serves as a reservoir, a site of dissemination, and an instigator for neurological sequelae during HIV-1 disease. Recent studies demonstrated that chemokine receptors are necessary coreceptors for HIV-1 entry which determine viral tropism for different cell types. To investigate the relative contribution of the β-chemokine receptors CCR3 and CCR5 to viral infection of mononuclear phagocytes we utilized a panel of macrophage-tropic HIV-1 strains (from blood and brain tissue) to infect highly purified populations of monocytes and microglia. Antibodies to CD4 (OKT4A) abrogated HIV-1 infection. The β chemokines and antibodies to CCR3 failed to affect viral infection of both macrophage cell types. Antibodies to CCR5 (3A9) prevented monocyte infection but only slowed HIV replication in microglia. Thus, CCR5, not CCR3, is an essential receptor for HIV-1 infection of monocytes. Microglia express both CCR5 and CCR3, but antibodies to them fail to inhibit viral entry, suggesting the presence of other chemokine receptors for infection of these cells. These studies demonstrate the importance of mononuclear phagocyte heterogeneity in establishing HIV-1 infection and persistence.

Human adipose cells express CD4, CXCR4, and CCR5 receptors: a new target cell type for the immunodeficiency virus‐1?

“…In this context, it has been recently shown that adipocytes and preadipocytes display macrophage-like characteristics (5) and monocytes/macrophages do not allow efficient entry of X4 strains, although they express both CXCR4 and CD4 (18,19). Nevertheless, R5 viruses infect monocyte/macrophage lineage efficiently (20,21), which was clearly not observed with adipocytes or preadipocytes, stressing the differences between the two cell types.…”

The role of infant immune responses and genetic factors in preventing HIV-1 acquisition and disease progression

“…Chemokines HIV-1 replication is suppressed in vitro by the CC chemokines, MIP-1 a , MIP-1 b and RANTES, and the CXC chemokine SDF-1 [29][30][31] when these natural ligands bind to CCR5 and CXCR4 cell surface receptors and block or down-regulate coreceptors utilized by HIV-1 [32][33][34][35]. While there has been controversy regarding the role of chemokines in vivo , the majority of clinical studies among HIV-1 infected adults suggest that increased MIP-1 a , MIP-1 b and RANTES protect against progression of HIV-1 to clinical AIDS [36][37][38][39][40].…”

The chemokine receptor CCR5 is not a necessary inflammatory mediator in kainic acid‐induced hippocampal injury: evidence for a compensatory effect by increased CCR2 and CCR3

“…Both CCR2 and CCR3 can be produced by neurons, microglia, leukocytes, and T cells. CCR2 can also be produced by astrocytes (Ghorpade et al 1998;Xia et al 1998;Klein et al 1999;Coughlan et al 2000;Huffnagle et al 2000;Chakravorty et al 2001;Fife et al 2001;Banisadr et al 2002). The fact that together CCR2-and CCR3-producing cells cover the whole range of CCR5-expressing cell types provides the possibility that MCP-2-CCR2/CCR3 can replace all the functions of MCP-2-CCR5 during KA-induced hippocampal injury.…”