Role Of Chemokine Receptors In Hiv-1 Infection And Pathogenesis

1999 ◽  
pp. 233-267 ◽  
Author(s):  
Ted M. Ross ◽  
Paul D. Bieniasz ◽  
Bryan R. Cullen
Keyword(s):  
Chemokine Receptors ◽  
Hiv 1

scholarly journals Chemokines: understanding their role in T-lymphocyte biology

1998 ◽  
Vol 333 (3) ◽  
pp. 457-470 ◽  
Author(s):  
Stephen G. WARD ◽  
John WESTWICK
Keyword(s):  
T Lymphocytes ◽  
Chemokine Receptors ◽  
Protein Tyrosine Kinase ◽  
Cell Function ◽  
Signalling Pathways ◽  
Cc Chemokine ◽  
Intracellular Signalling Pathways ◽  
And Function ◽  
Hiv 1

The chemokines are a complex superfamily of small, secreted proteins that were initially characterized through their chemotactic effects on a variety of leucocytes. The superfamily is divided into families based on structural and genetic considerations and have been termed the CXC, CC, C and CX3C families. Chemokines from these families have a key role in the recruitment and function of T lymphocytes. Moreover, T lymphocytes have also been identified as a source of a number of chemokines. T lymphocytes also express most of the known CXC and CC chemokine receptors to an extent that depends on their state of activation/differentiation and/or the activating stimuli. The expression of two chemokine receptors, namely CXCR4 and CCR5, together with the regulated production of their respective ligands, appears to be extremely important in determining sensitivity of T cells to HIV-1 infection. The intracellular events which mediate the effects of chemokines, particularly those elicited by the CC chemokine RANTES, include activation of both G-protein- and protein tyrosine kinase-coupled signalling pathways. The present review describes our current understanding of the structure and expression of chemokines and their receptors, the effects of chemokines on T-cell function(s), the intracellular signalling pathways activated by chemokines and the role of certain chemokines and chemokine receptors in determining sensitivity to HIV-1 infection.

scholarly journals Chemokines

2007 ◽  
Vol 7 ◽  
pp. 224-232 ◽  
Author(s):  
Richard Horuk
Keyword(s):  
Autoimmune Disease ◽  
Autoimmune Diseases ◽  
Chemokine Receptors ◽  
Short Review ◽  
Host Defence ◽  
Therapeutic Approaches ◽  
A Site ◽  
Hiv 1

Chemokines are a family of polypeptides that direct the migration of leukocytestoward a site of infection. They play a major role in autoimmune disease and chemokine receptors have recently been found to mediate HIV-1 fusion. In this short review we examine the role of chemokines in host defence and in the pathophysiology of autoimmune diseases. We conclude by discussing various therapeutic approaches that target chemokine receptors and that could be beneficial in disease.

scholarly journals Lineage-Specific Differences between the gp120 Inner Domain Layer 3 of Human Immunodeficiency Virus and That of Simian Immunodeficiency Virus

2016 ◽  
Vol 90 (22) ◽  
pp. 10065-10073 ◽  
Author(s):  
Shilei Ding ◽  
Halima Medjahed ◽  
Jérémie Prévost ◽  
Mathieu Coutu ◽  
Shi-Hua Xiang ◽  
...  
Keyword(s):  
Human Immunodeficiency Virus ◽  
Simian Immunodeficiency Virus ◽  
Conformational Changes ◽  
Viral Entry ◽  
Chemokine Receptors ◽  
Immunodeficiency Virus ◽  
Layer 2 ◽  
Hiv 1

ABSTRACT Binding of human immunodeficiency virus type 1 (HIV-1) and simian immunodeficiency virus (SIV) gp120 exterior envelope glycoprotein to CD4 triggers conformational changes in gp120 that promote its interaction with one of the chemokine receptors, usually CCR5, ultimately leading to gp41-mediated virus-cell membrane fusion and entry. We previously described that topological layers (layer 1, layer 2, and layer 3) in the gp120 inner domain contribute to gp120-trimer association in the unliganded state but also help secure CD4 binding. Relative to layer 1 of HIV-1 gp120, the SIVmac239 gp120 layer 1 plays a more prominent role in maintaining gp120-trimer association but is minimally involved in promoting CD4 binding, which could be explained by the existence of a well-conserved tryptophan at position 375 (Trp 375) in HIV-2/SIVsmm. In this study, we investigated the role of SIV layer 3 in viral entry, cell-to-cell fusion, and CD4 binding. We observed that a network of interactions involving some residues of the β8-α5 region in SIVmac239 layer 3 may contribute to CD4 binding by helping shape the nearby Phe 43 cavity, which directly contacts CD4. In summary, our results suggest that layer 3 in SIV has a greater impact on CD4 binding than in HIV-1. This work defines lineage-specific differences in layer 3 from HIV-1 and that from SIV. IMPORTANCE CD4-induced conformational changes in the gp120 inner domain involve rearrangements between three topological layers. While the role of layers 1 to 3 for HIV-1 and layers 1 and 2 for SIV on gp120 transition to the CD4-bound conformation has been reported, the role of SIV layer 3 remains unknown. Here we report that SIV layer 3 has a greater impact on CD4 binding than does layer 3 in HIV-1 gp120. This work defines lineage-specific differences in layer 3 from HIV-1 and SIV.

scholarly journals Mechanisms of HIV-1 evasion to the antiviral activity of chemokine CXCL12 indicate potential links with pathogenesis

2021 ◽  
Vol 17 (4) ◽  
pp. e1009526
Author(s):  
Marie Armani-Tourret ◽  
Zhicheng Zhou ◽  
Romain Gasser ◽  
Isabelle Staropoli ◽  
Vincent Cantaloube-Ferrieu ◽  
...  
Keyword(s):  
Chemokine Receptors ◽  
Neutralizing Antibodies ◽  
Effector Memory ◽  
Broadly Neutralizing Antibodies ◽  
Treatment Naïve ◽  
Chemokine Cxcl12 ◽  
Effector Memory Cells ◽  
Hiv 1

HIV-1 infects CD4 T lymphocytes (CD4TL) through binding the chemokine receptors CCR5 or CXCR4. CXCR4-using viruses are considered more pathogenic, linked to accelerated depletion of CD4TL and progression to AIDS. However, counterexamples to this paradigm are common, suggesting heterogeneity in the virulence of CXCR4-using viruses. Here, we investigated the role of the CXCR4 chemokine CXCL12 as a driving force behind virus virulence. In vitro, CXCL12 prevents HIV-1 from binding CXCR4 and entering CD4TL, but its role in HIV-1 transmission and propagation remains speculative. Through analysis of thirty envelope glycoproteins (Envs) from patients at different stages of infection, mostly treatment-naïve, we first interrogated whether sensitivity of viruses to inhibition by CXCL12 varies over time in infection. Results show that Envs resistant (RES) to CXCL12 are frequent in patients experiencing low CD4TL levels, most often late in infection, only rarely at the time of primary infection. Sensitivity assays to soluble CD4 or broadly neutralizing antibodies further showed that RES Envs adopt a more closed conformation with distinct antigenicity, compared to CXCL12-sensitive (SENS) Envs. At the level of the host cell, our results suggest that resistance is not due to improved fusion or binding to CD4, but owes to viruses using particular CXCR4 molecules weakly accessible to CXCL12. We finally asked whether the low CD4TL levels in patients are related to increased pathogenicity of RES viruses. Resistance actually provides viruses with an enhanced capacity to enter naive CD4TL when surrounded by CXCL12, which mirrors their situation in lymphoid organs, and to deplete bystander activated effector memory cells. Therefore, RES viruses seem more likely to deregulate CD4TL homeostasis. This work improves our understanding of the pathophysiology and the transmission of HIV-1 and suggests that RES viruses’ receptors could represent new therapeutic targets to help prevent CD4TL depletion in HIV+ patients on cART.

Role of Cations in the Interaction of Pradimicins with HIV-1 Envelope gp120

2013 ◽  
Vol 13 (16) ◽  
pp. 1907-1915 ◽  
Author(s):  
Bart Hoorelbeke ◽  
Youngju Kim ◽  
Toshikazu Oki ◽  
Yasuhiro Igarashi ◽  
Jan Balzarini
Keyword(s):  
Hiv 1 ◽  
Envelope Gp120

Role of HIV-1 Envelope Glycoproteins Conformation and Accessory Proteins on ADCC Responses

2015 ◽  
Vol 14 (1) ◽  
pp. 9-23 ◽  
Author(s):  
Maxime Veillette ◽  
Jonathan Richard ◽  
Marzena Pazgier ◽  
George K. Lewis ◽  
Matthew S. Parsons ◽  
...  
Keyword(s):  
Envelope Glycoproteins ◽  
Accessory Proteins ◽  
Hiv 1

Pivotal Role of the Genital Epithelial Cells in HIV-1 Transmission

2015 ◽  
Vol 13 (6) ◽  
pp. 479-489
Author(s):  
Amelie Saint Jean ◽  
Thomas Bourlet ◽  
Olivier Delezay
Keyword(s):  
Epithelial Cells ◽  
Pivotal Role ◽  
Hiv 1

scholarly journals The Role of Capsid in HIV-1 Nuclear Entry

Viruses ◽  
2021 ◽  
Vol 13 (8) ◽  
pp. 1425
Author(s):  
Anabel Guedán ◽  
Eve R. Caroe ◽  
Genevieve C. R. Barr ◽  
Kate N. Bishop
Keyword(s):  
Nuclear Pore ◽  
Outer Face ◽  
Nuclear Entry ◽  
Nuclear Compartment ◽  
Critical Step ◽  
Technological Advances ◽  
Dividing Cells ◽  
Hiv 1 ◽  
Gain Access

HIV-1 can infect non-dividing cells. The nuclear envelope therefore represents a barrier that HIV-1 must traverse in order to gain access to the host cell chromatin for integration. Hence, nuclear entry is a critical step in the early stages of HIV-1 replication. Following membrane fusion, the viral capsid (CA) lattice, which forms the outer face of the retroviral core, makes numerous interactions with cellular proteins that orchestrate the progress of HIV-1 through the replication cycle. The ability of CA to interact with nuclear pore proteins and other host factors around the nuclear pore determines whether nuclear entry occurs. Uncoating, the process by which the CA lattice opens and/or disassembles, is another critical step that must occur prior to integration. Both early and delayed uncoating have detrimental effects on viral infectivity. How uncoating relates to nuclear entry is currently hotly debated. Recent technological advances have led to intense discussions about the timing, location, and requirements for uncoating and have prompted the field to consider alternative uncoating scenarios that presently focus on uncoating at the nuclear pore and within the nuclear compartment. This review describes recent advances in the study of HIV-1 nuclear entry, outlines the interactions of the retroviral CA protein, and discusses the challenges of investigating HIV-1 uncoating.

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