Predominance of the heterozygous <scp>CCR</scp>5 delta‐24 deletion in African individuals resistant to <scp>HIV</scp> infection might be related to a defect in <scp>CCR</scp>5 addressing at the cell surface

Arendt, Vic; Amand, Mathieu; Iserentant, Gilles; Lemaire, Morgane; Masquelier, Cécile; Ndayisaba, Gilles; Verhofstede, Chris; Karita, Etienne; Allen, Susan; Chevigné, Andy; Schmit, Jean-Claude; Perez-Bercoff, Danielle; Seguin-Devaux, Carole

doi:10.1002/jia2.25384

Cited by 11 publications

(31 citation statements)

References 80 publications

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“…With respect to CCR5, the 32 bp deletion occurring in Caucasians is however not the only mutation known to alter the molecule's expression and/or function. A novel 24-base pair deletion with phenotypic effects similar to that of CCR5∆32 was recently reported in the coding region of CCR5 in African individuals [41]. Numerous other genetic mutations within the CCR5 gene structure have been studied and linked to disease progression [42][43][44][45][46].…”

Section: Introductionmentioning

confidence: 93%

Metabolomics as an Approach to Characterise the Contrasting Roles of CCR5 in the Presence and Absence of Disease

Rautenbach

Williams

2020

IJMS

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Chemokine receptors such as C-C chemokine receptor 5 (CCR5) are activated through interaction with their ligands and are well known for their role in chemotaxis and signal transduction. While serving these roles, cellular responses are effected, hence the immune function of these molecules is established. Given the role of CCR5 in immune function and that the immune and metabolic systems are interlinked, subsequent immune-directed changes should be measurable at a metabolic level. Numerous investigations have reported on metabolic changes associated with CCR5 status in the presence of disease, so as to understand whether specific CCR5 genotypes, frequency and/or levels offer protection to the host or not. However, these metabolic changes were recorded using older conventional techniques. Depending on certain factors such as the disease model, the geography of the samples and/or the ethnic group under study, the role of CCR5 in disease differs. In addition, little is known about CCR5’s role in the absence of an enhanced inflammatory state, such as when infection persists. Metabolomics is defined as the study of metabolites and informs on metabolic changes within living organisms as induced by various stimuli, such as the interaction of CCR5 with its ligand. Since metabolomics reflects the underlying biochemical activity and state of cells/tissues, this review proposes it as a tool to clarify the contrasting roles of CCR5.

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Section: Introductionmentioning

confidence: 93%

Metabolomics as an Approach to Characterise the Contrasting Roles of CCR5 in the Presence and Absence of Disease

Rautenbach

Williams

2020

IJMS

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“…Compounds 2, 6-14, and 21-28 were tested against HIV-1 while using a pseudotype virus assay allowing only one cycle of viral replication and being more sensitive for compounds targeting the early steps of HIV replication, such as reverse transcription and integration [25]. Tetrahydroprotoapigenone (9) was found to inhibit viral infection by ca.…”

Section: Antiretroviral Activitymentioning

confidence: 99%

“…1 serum (Lonza, Maastricht, The Netherlands) supplemented with 2 mM l-glutamine, 100 units/mL of penicillin, and 100 µg/mL streptomycin (Invitrogen, Merelbeke, Belgium). Pseudotyped viral particules bearing the ADA HIV Env were produced, as described previously [25].…”

Section: Structure Elucidationmentioning

confidence: 99%

“…Antiviral activity was assessed while using a Pseudotype Virus Assay, allowing for one cycle of viral replication [25]. The U373-CD4-CCR5 cells were infected by pseudotyped virus pNL4.3∆envLuc-ADA 8 using spinoculation at 1200 g during 2 h in the presence of compounds and cultured for two consecutive days in the presence of the compounds.…”

Section: Anti-hiv Testingmentioning

confidence: 99%

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Less Cytotoxic Protoflavones as Antiviral Agents: Protoapigenone 1′-O-isopropyl ether Shows Improved Selectivity Against the Epstein–Barr Virus Lytic Cycle

Vágvölgyi

Girst

Kúsz

et al. 2019

IJMS

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Protoflavones, a rare group of natural flavonoids with a non-aromatic B-ring, are best known for their antitumor properties. The protoflavone B-ring is a versatile moiety that might be explored for various pharmacological purposes, but the common cytotoxicity of these compounds is a limitation to such efforts. Protoapigenone was previously found to be active against the lytic cycle of Epstein–Barr virus (EBV). Further, the 5-hydroxyflavone moiety is a known pharmacophore against HIV-integrase. The aim of this work was to prepare a series of less cytotoxic protoflavone analogs and study their antiviral activity against HIV and EBV. Twenty-seven compounds, including 18 new derivatives, were prepared from apigenin through oxidative de-aromatization and subsequent continuous-flow hydrogenation, deuteration, and/or 4′-oxime formation. One compound was active against HIV at the micromolar range, and three compounds showed significant activity against the EBV lytic cycle at the medium-low nanomolar range. Among these derivatives, protoapigenone 1′-O-isopropyl ether (6) was identified as a promising lead that had a 73-times selectivity of antiviral over cytotoxic activity, which exceeds the selectivity of protoapigenone by 2.4-times. Our results open new opportunities for designing novel potent and safe anti-EBV agents that are based on the natural protoflavone moiety.

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“…For example, in Trypanosoma cruzi infection, several CCR5 polymorphisms (rs333, rs3176763, rs11575815, rs1799988, rs1800024, rs2856758) were associated to differential clinical outcomes (Batista et al, 2018; Calzada, Nieto, Beraún, & Martín, 2001; Flórez, Martín, & González, 2012; Frade et al, 2013; Machuca, Suárez, Echeverría, Martín, & González, 2014; Nogueira et al, 2012; Oliveira et al, 2015, 2016). Recently, a genetic variant similar to CCR5Δ32, called CCR5Δ24, has been associated with HIV protection in the African population (Arendt et al, 2019). This latter polymorphism also affects the expression of CCR5 on the cell surface and, therefore, may have functional effects in African populations, similar to CCR5Δ32 in Euro‐descendant individuals.…”

Section: Introductionmentioning

confidence: 99%

CCR5 and CCR5Δ32 in bacterial and parasitic infections: Thinking chemokine receptors outside the HIV box

Ellwanger

Kaminski

Rodrigues

et al. 2020

Int J Immunogenetics

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The CCR5 molecule was reported in 1996 as the main HIV‐1 co‐receptor. In that same year, the CCR5Δ32 genetic variant was described as a strong protective factor against HIV‐1 infection. These findings led to extensive research regarding the CCR5, culminating in critical scientific advances, such as the development of CCR5 inhibitors for the treatment of HIV infection. Recently, the research landscape surrounding CCR5 has begun to change. Different research groups have realized that, since CCR5 has such important effects in the chemokine system, it could also affect other different physiological systems. Therefore, the effect of reduced CCR5 expression due to the presence of the CCR5Δ32 variant began to be further studied. Several studies have investigated the role of CCR5 and the impacts of CCR5Δ32 on autoimmune and inflammatory diseases, various types of cancer, and viral diseases. However, the role of CCR5 in diseases caused by bacteria and parasites is still poorly understood. Therefore, the aim of this article is to review the role of CCR5 and the effects of CCR5Δ32 on bacterial (brucellosis, osteomyelitis, pneumonia, tuberculosis and infection by Chlamydia trachomatis) and parasitic infections (toxoplasmosis, leishmaniasis, Chagas disease and schistosomiasis). Basic information about each of these infections was also addressed. The neglected role of CCR5 in fungal disease and emerging studies regarding the action of CCR5 on regulatory T cells are briefly covered in this review. Considering the “renaissance of CCR5 research,” this article is useful for updating researchers who develop studies involving CCR5 and CCR5Δ32 in different infectious diseases.

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Predominance of the heterozygous CCR5 delta‐24 deletion in African individuals resistant to HIV infection might be related to a defect in CCR5 addressing at the cell surface

Cited by 11 publications

References 80 publications

Metabolomics as an Approach to Characterise the Contrasting Roles of CCR5 in the Presence and Absence of Disease

Metabolomics as an Approach to Characterise the Contrasting Roles of CCR5 in the Presence and Absence of Disease

Less Cytotoxic Protoflavones as Antiviral Agents: Protoapigenone 1′-O-isopropyl ether Shows Improved Selectivity Against the Epstein–Barr Virus Lytic Cycle

CCR5 and CCR5Δ32 in bacterial and parasitic infections: Thinking chemokine receptors outside the HIV box

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