Lack of p56  lck expression correlates with CD4 endocytosis in primary lymphoid and myeloid cells

Pelchen–Matthews, Annegret; Silva, Rosângela P. da; Bijlmakers, Marie-José; Signoret, Nathalie; Gordon, Siamon; Marsh, Mark

doi:10.1002/(sici)1521-4141(199811)28:11<3639::aid-immu3639>3.0.co;2-q

Cited by 44 publications

(46 citation statements)

References 33 publications

(43 reference statements)

Supporting

Mentioning

Contrasting

Order By: Relevance

“…It is possible that co-engagement of CD4 along with the chemokine receptor may cooperate to initiate unique signals not elicited by either receptor alone, or that CD4-initiated signals may modify signals initiated by chemokine receptor stimulation, as occurs with CD4 and the TCR in lymphocytes (33). Although the CD4-associated T cell tyrosine kinase p56 lck is not expressed in macrophages (34), gp120 binding of macrophage CD4 may activate other pathways (35). However, antibody engagement of macrophage CD4, followed by SDF-1␣ or MIP-1␤ stimulation, did not elicit a NSC current (data not shown).…”

Section: Discussionmentioning

confidence: 99%

HIV-1 gp120 and chemokines activate ion channels in primary macrophages through CCR5 and CXCR4 stimulation

Liu

Williams²,

McManus³

et al. 2000

Proc. Natl. Acad. Sci. U.S.A.

140

130

View full text Add to dashboard Cite

HIV type 1 (HIV-1) uses the chemokine receptors CCR5 and CXCR4 as coreceptors for entry into target cells. Here we show that the HIV-1 envelope gp120 (Env) activates multiple ionic signaling responses in primary human macrophages, which are important targets for HIV-1 in vivo. Env from both CCR5-dependent JRFL (R5) and CXCR4-dependent IIIB (X4) HIV-1 opened calcium-activated potassium (K Ca), chloride, and calcium-permeant nonselective cation channels in macrophages. These signals were mediated by CCR5 and CXCR4 because macrophages lacking CCR5 failed to respond to JRFL and an inhibitor of CXCR4 blocked ion current activation by IIIB. MIP-1␤ and SDF-1␣, chemokine ligands for CCR5 and CXCR4, respectively, also activated K Ca and Cl ؊ currents in macrophages, but nonselective cation channel activation was unique to gp120. Intracellular Ca 2؉ levels were also elevated by gp120. The patterns of activation mediated by CCR5 and CXCR4 were qualitatively similar but quantitatively distinct, as R5 Env activated the K Ca current more frequently, elicited Cl ؊ currents that were Ϸ2-fold greater in amplitude, and elevated intracellular Ca ؉2 to higher peak and steady-state levels. Env from R5 and X4 primary isolates evoked similar current responses as the corresponding prototype strains. Thus, the interaction of HIV-1 gp120 with CCR5 or CXCR4 evokes complex and distinct signaling responses in primary macrophages, and gp120-evoked signals differ from those activated by the coreceptors' chemokine ligands. Intracellular signaling responses of macrophages to HIV-1 may modulate postentry steps of infection and cell functions apart from infection.

show abstract

Section: Discussionmentioning

confidence: 99%

HIV-1 gp120 and chemokines activate ion channels in primary macrophages through CCR5 and CXCR4 stimulation

Liu

Williams²,

McManus³

et al. 2000

Proc. Natl. Acad. Sci. U.S.A.

140

130

View full text Add to dashboard Cite

show abstract

“…Several experiments examining the mechanism of Nef-dependent CD4 transport have been performed with adherent cell lines that do not express Lck, a primary regulator of normal CD4 surface expression (104,106,107,(117)(118)(119)(120)(121). There is evidence that nonlymphoid cells (and lymphoid cells lacking Lck) constitutively internalize and recycle CD4, whereas in T cells, the expression of Lck anchors CD4 to the cell membrane (117,120).…”

Section: The Nef Flexible Loop and Its Binding Partnersmentioning

confidence: 99%

Human Immunodeficiency Virus Type 1 Nef: Adapting to Intracellular Trafficking Pathways

Roeth¹,

Collins

2006

Microbiol Mol Biol Rev

168

156

View full text Add to dashboard Cite

SUMMARY The Nef protein of primate lentiviruses is a unique protein that has evolved in several ways to manipulate the biology of an infected cell to support viral replication, immune evasion, pathogenesis, and viral spread. Nef is a small (25- to 34-kDa), myristoylated protein that binds to a collection of cellular factors and acts as an adaptor to generate novel protein interactions to accomplish specific functions. Of the many biological activities attributed to Nef, the reduction of surface levels of the viral receptor (CD4) and antigen-presenting molecules (major histocompatibility complex class I) has been intensely examined; recent evidence demonstrates that Nef utilizes multiple, distinct pathways to affect these proteins. To accomplish this, Nef promotes the formation of multiprotein complexes, recruiting host adaptor proteins to commandeer intracellular vesicular trafficking routes. The altered trafficking of several other host molecules has also been reported, and an emerging theory suggests that Nef generates pleiotrophic effects in the secretory and endocytic pathways that reprogram intracellular protein trafficking and may ultimately provide an efficient platform for viral assembly. This review critically discusses some of the major findings regarding the impact of human immunodeficiency virus type 1 Nef on host protein transport and addresses some emerging directions in this area of human immunodeficiency virus biology.

show abstract

“…Goat anti-human IgG-FITC was purchased from Perbio Science United Kingdom (Cheshire, United Kingdom). Q4120 was radioiodinated using 125 I-labeled 3-(p-hydroxyphenyl)-propionic acid N-hydroxy-succinimide ester (Bolton and Hunter reagent) essentially as described (Pelchen-Matthews et al, 1998). Specific activity was ϳ500 Ci/mmol.…”

mentioning

confidence: 99%

A Conserved Dileucine Motif Mediates Clathrin and AP-2–dependent Endocytosis of the HIV-1 Envelope Protein

Byland

Vance

Hoxie

et al. 2007

MBoC

Self Cite

124

133

View full text Add to dashboard Cite

During the assembly of enveloped viruses viral and cellular components essential for infectious particles must colocalize at specific membrane locations. For the human and simian immunodeficiency viruses (HIV and SIV), sorting of the viral envelope proteins (Env) to assembly sites is directed by trafficking signals located in the cytoplasmic domain of the transmembrane protein gp41 (TM). A membrane proximal conserved GYxxØ motif mediates endocytosis through interaction with the clathrin adaptor AP-2. However, experiments with SIV mac239 Env indicate the presence of additional signals. Here we show that a conserved C-terminal dileucine in HIV HxB2 also mediates endocytosis. Biochemical and morphological assays demonstrate that the C-terminal dileucine motif mediates internalization as efficiently as the GYxxØ motif and that both must be removed to prevent Env internalization. RNAi experiments show that depletion of the clathrin adaptor AP-2 leads to increased plasma membrane expression of HIV Env and that this adaptor is required for efficient internalization mediated by both signals. The redundancy of conserved endocytosis signals and the role of the SIV mac239 Env GYxxØ motif in SIV pathogenesis, suggest that these motifs have functions in addition to endocytosis, possibly related to Env delivery to the site of viral assembly and/or incorporation into budding virions. INTRODUCTIONThe assembly of enveloped animal viruses requires that the viral and cellular components needed to make infectious particles are brought to the same site within the infected cell at the same time. For the primate lentiviruses (the human immunodeficiency viruses types 1 and 2 [HIV-1 and -2] and the simian immunodeficiency viruses [SIV]) the key viral structural proteins required to generate infectious particles are Gag, Gag-Pol, and Env. Although Gag alone can promote the formation of virus-like particles, Env and Gag-Pol are both essential for the formation of infectious virions. Although a considerable amount is known about these proteins, little is understood of the mechanisms through which they are targeted to the sites of assembly in infected cells.In many cell types, HIV assembles at the plasma membrane and, in the course of Gag assembly, the particles derive their membrane from the plasma membrane. For these particles to be infectious, Env must be transported to the cell surface, but the level to which it is incorporated into budding virions is unclear. Recent data have suggested that fewer than 10 Env protein complexes (trimers) are incorporated per virion (Chertova et al., 2002;Zhu et al., 2003), and early studies of HIV infected T-cells showed that much of the newly synthesized Env is transported to lysosomes and degraded (Willey et al., 1988). However, it has recently become evident that in macrophages the assembly of Envcontaining infectious HIV occurs on intracellular membranes, that have some characteristics in common with late endosomes (Raposo et al., 2002;Pelchen-Matthews et al., 2003). The assembly of virus in distinct...

show abstract

Lack of p56 lck expression correlates with CD4 endocytosis in primary lymphoid and myeloid cells

Cited by 44 publications

References 33 publications

HIV-1 gp120 and chemokines activate ion channels in primary macrophages through CCR5 and CXCR4 stimulation

HIV-1 gp120 and chemokines activate ion channels in primary macrophages through CCR5 and CXCR4 stimulation

Human Immunodeficiency Virus Type 1 Nef: Adapting to Intracellular Trafficking Pathways

A Conserved Dileucine Motif Mediates Clathrin and AP-2–dependent Endocytosis of the HIV-1 Envelope Protein

Contact Info

Product

Resources

About