Chemokines and Chemokine Receptors: Accomplices for Human Immunodeficiency Virus Infection and Latency

Abstract

Chemokines are small chemotactic cytokines that are involved in the regulation of immune cell migration. Multiple functional properties of chemokines, such as pro-inflammation, immune regulation, and promotion of cell growth, angiogenesis, and apoptosis, have been identified in many pathological and physiological contexts. Human immunodeficiency virus (HIV) infection is characterized by persistent inflammation and immune activation during both acute and chronic phases, and the “cytokine storm” is one of the hallmarks of HIV infection. Along with immune activation after HIV infection, an extensive range of chemokines and other cytokines are elevated, thereby generating the so-called “cytokine storm.” In this review, the effects of the upregulated chemokines and chemokine receptors on the processes of HIV infection are discussed. The objective of this review was to focus on the main chemokines and chemokine receptors that have been found to be associated with HIV infection and latency. Elevated chemokines and chemokine receptors have been shown to play important roles in the HIV life cycle, disease progression, and HIV reservoir establishment. Thus, targeting these chemokines and receptors and the other proteins of related signaling pathways might provide novel therapeutic strategies, and the evidence indicates a promising future regarding the development of a functional cure for HIV.

HIV-1 Envelope Glycoproteins Induce the Production of TNF-α and IL-10 in Human Monocytes by Activating Calcium Pathway

“…Several other studies have shown that, in addition to TNF-α and IL-10, HIV-1 enveloped glycoproteins also stimulate the production of a variety of pro-inflammatory and anti-inflammatory cytokines/chemokines, including IL-1β, IL-6, IL-8, IL-18, IL-23, IL-27, CCL2, CCL4, CCL20, CXCL2, CXCL13, and TSLP 62 – 64 that are also implicated in HIV-1 associated impairment of the immune system 52 , 53 , 63 , AIDS-related diseases, and the aberrant sustained hyper immune-activation 65 , 66 .…”

High circulating SDF-1and MCP-1 levels and genetic variations in CXCL12, CCL2 and CCR5: Prognostic signature of immune recovery status in treated HIV-positive patients

“…SDF-1/CXCL12 is the most primitive chemokine that regulates development in multiple systems and diverse cell functions, including proliferation and survival in the immune system, through the two known receptors CXCR4 and ACKR3. [13,15,20] Interestingly, the affinity of CXCL12/SDF-1 for CXCR4 correlates well with its action as a suppressor of infection by T-tropic HIV-1 species and its ability to induce CXCR4 internalization. [21] In this context, the observed adverse effect of SDF-1 gene expression on the natural history of HIV-1 disease could be explained by the fact that the SDF-1À3 0 T allele was more likely to be associated with detectable X4-tropic viruses.…”

Insight on the regulation of chemokine activities

“…In HIV‐1 infection, chemokine receptors are used as co‐receptor for viral entry, the virus hijacks the cytoskeleton machinery to favor integration in the host genome, and can alter chemokine production. Wang and colleagues have recently published a comprehensive review, on the role of chemokines and chemokine receptors in the pathogenesis of HIV‐1 infection . In this chapter, we discuss how alterations, induced by chronic immune activation associated to the viral infection, can blunt the responses of T cells to chemokines.…”