Recently, Siglec-1 was shown to facilitate HIV-1 infection of DCs and macrophages by binding to the sialoglycans on the gp120 envelope. Other unique cellular molecules, such as α4β7, tetraspanins, and heparan sulfate proteoglycans, have a role in HIV-1 infection. However, unlike CD4 + T cells, macrophages and MDMs express relatively low levels of surface CD4, thus, confounding the role of this molecule in HIV-1 entry in macrophages. ĬD4 molecules and chemokine receptors are the major receptor/coreceptors used by HIV-1 for infection of target cells. M2 macrophages secrete IL-10, express scavenger and mannose receptors, contribute to Th2 responses, enhance phagocytosis, eliminate parasites, and promote tissue repair. M1 macrophages produce IL-1β, IL-12, IL-23, and TNF-α, as well as reactive oxygen and nitrogen intermediates support Th1 responses and mediate resistance to tumors and intracellular pathogens. GM-CSF and M-CSF are macrophage growth factors that have distinct effects on macrophage differentiation, resulting in either the M1 or the M2 phenotype.
Macrophages exhibit phenotypic heterogeneity that is dependent upon the cytokines present within their environment. Following in vitro stimulation with various stimuli, M2 macrophages are further divided into 3 subtypes (M2a, M2b, and M2c). Generally, macrophages are classified into 2 types, classically activated (M1) and alternatively activated (M2) macrophages. In humans, macrophages arise from circulating or resident monocytes, and their differentiation and effector functions are largely dependent on the surrounding microenvironment. Macrophages are targets of HIV-1 and represent a potentially long-lived viral reservoir. These results highlight the importance of sialic acids on the V1V2 region in binding to sialic acid-binding immunoglobulin-like lectin and suggest that the unusually long surface-exposed sialic acid-binding immunoglobulin-like lectin might aid in the capture and entry of human immunodeficiency virus type 1 into monocyte–derived macrophages.
Removal of sialic acid residues or glycans from scaffolded V1V2 protein decreased human immunodeficiency virus type 1 infectivity. Furthermore, sialic acid residues present in the V1V2 region of the envelope protein mediated human immunodeficiency virus type 1 interaction with sialic acid-binding immunoglobulin-like lectin and entry into macrophage colony-stimulating factor–derived monocyte–derived macrophages. Anti-sialic acid-binding immunoglobulin-like lectin, trimeric glycoprotein 145, and scaffolded V1V2 proteins were bound to sialic acid-binding immunoglobulin-like lectin and significantly reduced human immunodeficiency virus type 1 entry and infection. Single-genome analysis and quantitative reverse transcriptase-polymerase chain reaction revealed that the differences in infectivity was not due to differences in viral fitness or in viral variants with differential infectivity but was due to reduced viral entry into the granulocyte macrophage colony-stimulating factor–derived monocyte–derived macrophages.
The number of sialic acid-binding immunoglobulin-like lectin receptors on macrophage colony-stimulating factor–derived monocyte–derived macrophages was significantly greater than on granulocyte macrophage colony-stimulating factor–derived monocyte–derived macrophages, and correspondingly, human immunodeficiency virus type 1 infection was greater in the macrophage colony-stimulating factor–derived monocyte–derived macrophages. Human immunodeficiency virus type 1 infection of monocyte–derived macrophages derived from granulocyte macrophage and macrophage colony-stimulating factors was predominantly facilitated by the sialic acid-binding immunoglobulin-like lectin-1. We report that growth factors, such as granulocyte macrophage colony-stimulating factor and macrophage colony-stimulating factor affect the phenotypic profile and permissiveness of macrophages to human immunodeficiency virus type 1. Macrophages have a critical role in human immunodeficiency virus type 1 transmission however, the mechanism or mechanisms of virus infection are poorly understood. Despite this, macrophages can be effectively infected with human immunodeficiency virus type 1. Monocytes and monocyte–derived macrophages express relatively low levels of CD4.
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