Polymorphic chemokine receptor and ligand genes in HIV infection

Introduction: There is growing evidence that polymorphisms in chemokine and chemokine receptor genes influence susceptibility to HIV infection and disease progression. However, not much is documented about the prevalence and effects of chemokine and chemokine receptor gene variations in the Zimbabwean population despite the high burden of HIV/AIDS in the country. This study therefore describes polymorphisms in CCR2, CX3CR1, SDF1 and RANTES genes in a Zimbabwean pediatric population and their effects on HIV infection in children born to HIV-infected mothers. Methodology: A total of 106 children between seven and nine years of age comprising 70 perinatally exposed to HIV (34 born infected [EI] and 36 born uninfected [EU]) and 36 unexposed and uninfected (UEUI) controls were recruited. Six allelic variants in four genes were genotyped using PCR-RFLP and sequencing. Results: Frequencies for minor alleles in the HIV uninfected groups (EU and UEUI) were CCR2 190A (16%), SDF1 801A (2%), CX3CR1 745A (9%), CX3CR1 839T (0%), RANTES In 1.1C (20%), and RANTES -403A (44%). There were significant differences between the EI and EU groups in the distribution of CCR2 190G/A genotype (15% versus 39%, respectively, p = 0.02) and CCR2 190G/A-CX3CR1 745G/G genotype combination (0% versus 33%, respectively, p = 0.002). Conclusions: Our findings suggest that chemokine and chemokine receptor gene variants seem to play an important role in the dynamics of HIV infection and could be used as drug or vaccine targets.

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Pushing it back. Dating the CCR5–32 bp deletion to the Mesolithic in Sweden and its implications for the Meso\Neo transition

Documenta Praehistorica ◽

10.4312/dp.33.5 ◽

2006 ◽

Vol 33 ◽

pp. 29-37 ◽

Cited By ~ 5

Author(s):

Kerstin Lidén ◽

Anna Linderholm ◽

Anders Götherström

Keyword(s):

Genetic Variation ◽

Hiv Infection ◽

Geographic Distribution ◽

Chemokine Receptor ◽

Receptor Gene ◽

Scientific Interest ◽

Swedish Population ◽

14Th Century ◽

Mesolithic Period ◽

Chemokine Receptor Gene

Genetic variation in the chemokine receptor gene CCR5 has received considerable scientific interest during the last few years. Protection against HIV-infection and AIDS, together with specific geographic distribution are the major reasons for the great interest in CCR5 32bp deletion. The event for the occurrence of this mutation has been postulated by coalescence dating to the 14th century, or 5000 BP. In our prehistoric Swedish samples we show that the frequency of 32pb deletion in CCR5 in the Neolithic population does not deviate from the frequency in a modern Swedish population, and that the deletion existed in Sweden already during the Mesolithic period.

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Lead Screening for CXCR4 of the Human HIV Infection Receptor Inhibited by Traditional Chinese Medicine

BioMed Research International ◽

10.1155/2014/809816 ◽

2014 ◽

Vol 2014 ◽

pp. 1-13

Author(s):

Tzu-Chieh Hung ◽

Wen-Yuan Lee ◽

Kuen-Bao Chen ◽

Calvin Yu-Chian Chen

Keyword(s):

Molecular Dynamics ◽

Chinese Medicine ◽

Traditional Chinese Medicine ◽

Hiv Infection ◽

Chemokine Receptor ◽

Hydrophobic Interactions ◽

Protein Ligand Interactions ◽

Ligand Interactions ◽

Acquired Immunodeficiency ◽

Immunodeficiency Syndrome

The acquired immunodeficiency syndrome (AIDS) is a serious worldwide disease caused by the human immunodeficiency virus (HIV) infection. Recent research has pointed out that the G protein-coupled chemokine receptor CXCR4 and the coreceptor C-C chemokine receptor type 5 (CCR5) are important targets for HIV infection. The traditional Chinese medicine (TCM) database has been screened for candidate compounds by simulating molecular docking and molecular dynamics against HIV. Saussureamine C, 5-hydroxy-L-tryptophan, and diiodotyrosine are selected based on the highest docking score. The molecular dynamics is helpful in the analysis and detection of protein-ligand interactions. According to the analysis of docking poses, hydrophobic interactions, hydrogen bond variations, and the comparison of the effect on CXCR4 and CCR5, these results indicate Saussureamine C may have better effect on these two receptors. But for some considerations, diiodotyrosine could make the largest variation and may have some efficacy contrary to expectations.

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A Novel Chemokine-Receptor-5 (CCR5) Blocker, SCH532706, Has Differential Effects on CCR5+CD4+and CCR5+CD8+T Cell Numbers in Chronic HIV Infection

AIDS Research and Human Retroviruses ◽

10.1089/aid.2009.0278 ◽

2010 ◽

Vol 26 (6) ◽

pp. 653-661 ◽

Cited By ~ 9

Author(s):

Sarah L. Pett ◽

John Zaunders ◽

Michelle Bailey ◽

John Murray ◽

Karen MacRae ◽

...

Keyword(s):

T Cell ◽

Hiv Infection ◽

Chemokine Receptor ◽

Cd8 T Cell ◽

Differential Effects ◽

Cell Numbers ◽

Chronic Hiv Infection ◽

Chemokine Receptor 5

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Reported CCR5-∆32 deviation from Hardy-Weinberg equilibrium is explained by poor genotyping of rs62625034

10.1101/791517 ◽

2019 ◽

Cited By ~ 1

Author(s):

Yosuke Tanigawa ◽

Manuel A. Rivas

Keyword(s):

Hiv Infection ◽

Chemokine Receptor ◽

Survival Probability ◽

Gene Editing ◽

Nature Medicine ◽

The Other ◽

Ccr5 Chemokine Receptor ◽

Weinberg Equilibrium ◽

Ethical Concerns ◽

Hardy Weinberg Equilibrium

AbstractIn the fall of 2018, news broke about a researcher from China who had used CRISPR gene editing to cause human babies to have a deletion in the CCR5 chemokine receptor, making them resistant to HIV infection. One of the numerous ethical concerns about this study is that the deletion may have other effects. Subsequently, Nature Medicine published a Brief Communications from Wei and Nielsen concluding that homozygotes for the CCR5-∆32 deletion have a survival probability to age 76 of 83.5% compared to 86.5% and 86.4% for the heterozygotes and the other homozygote, respectively, and that observed departures from Hardy Weinberg proportions also support selection operating on this allele1. In the study, Wei and Nielsen used a proxy variant, rs62625034 in their analysis. Here, we report that the reported CCR5-∆32 deviation from Hardy-Weinberg equilibrium (HWE) inferred by Wei and Nielsen can be explained by poor genotyping of rs62625034, the variant used for their analysis.

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