[Full text] The role of the human Duffy antigen receptor for chemokines in malari | JRLCR
Interest in the global prevalence of the Duffy blood group variants is by the Duffy-negative phenotype against Plasmodium vivax infection. Duffy antigen/chemokine receptor (DARC), also known as Fy glycoprotein (FY) or CD (Cluster of Differentiation ), is a protein that in humans is encoded by the DARC gene. The Duffy antigen is located on the surface of red blood cells, and is named .. The association between the Duffy antigen and HIV infection appears to be. The Duffy blood group antigen serves not only as blood group antigen, but also as a receptor for a Plasmodium vivax (P. vivax) causes approximately between 70 and 80 million cases of malaria per population living in a malaria endemic region of Papua .. P. vivax is directly related to the Fy(a 2 b 2).
It shares structural similarity with G-protein coupled receptors but so far, it has not been shown to be a member of this family.
Duffy blood group and malaria.
The binding site for chemokines, the binding site for P. Getting down to malarial nuts and bolts: Conserved residues in the Plasmodium vivax Duffy-binding protein ligand domain are critical for erythrocyte receptor recognition. PMC ] [ PubMed: The Duffy blood groups, vivax malaria, and malaria selection in human populations: Speculations on the origins of Plasmodium vivax malaria.
Mohandas NNarla A. Blood group antigens in health and disease. Deletion of the murine Duffy gene Dfy reveals that the Duffy receptor is functionally redundant. Study of anti-Fya in five black Fy a-b- patients.Duffy
Delayed hemolytic transfusion reaction due to anti-Fyb caused by a primary immune response: The second example of anti-Duffy5. Delayed haemolytic transfusion reaction due to simultaneous appearance of anti-Fya and Anti-Fy5. Haemolytic disease of the fetus and newborn due to anti-Fy a and the potential clinical value of Duffy genotyping in pregnancies at risk. Vaccines as a therapeutic tool Vaccines are considered the best means of control of infectious diseases. Over 70 different vaccines against P.
The most promising vaccine against P. Unfortunately, the same advances have not been seen for vaccines against P.
A series of P. These include the apical membrane antigen AMA-198 DBP, 99reticulocyte binding proteins,and merozoite surface proteins. Because of the difficulty in obtaining enough reticulocytes, long-term culture for P. Despite these challenges, a number of potential strategies are being explored for the development of a P.
Duffy blood group and malaria.
Some studies have reported strategies to overcoming strain-specific immunity in P. Notwithstanding, the efficacy of a DBP-based vaccine may differ among populations with varying Fy phenotypes. Several chemokine receptors have been validated as successful targets of anti-inflammatory therapies and anti-HIV infectivity strategy. A new biotechnology tool for genome editing, CRISPR, has gained wide interest in the scientific world and researchers believe that it could transform the field of biology.
An example is engineered monkeys with targeted mutations to prevent HIV infections in human cells. An alternate DARC-related approach to vaccines is the use of novel agents specific for individual malaria species targeting their pathways of invasion.
Zinc finger array precursors of zinc finger nucleases, which are artificial hybrid restriction enzymes, are becoming powerful tools for primary editing of host genomes as a strategy to halt pathogen infectivity.
The feasibility of this approach is supported by existing evidence pointing to resistance of RBCs of naturally selected Duffy-negative blacks to P. Small molecule agonists and antagonists as inhibitors of receptor-ligand interaction The interaction between chemokine receptors and their ligands involves initial interaction with the N-terminal extracellular domains of the receptor, generally mediated by electrostatic forces.
Modifications of these regions, using chemokine analogues, either truncations or extension of the amino terminus, — have been found to retain affinity for the receptors, while impairing signaling. Chemokine receptor antagonists are still in early stages of development.
Through screening of small molecules, Pfizer was able to identify a small molecule inhibitor that could block the gp binding to the chemokine receptor CCR5. However, TAK, an antagonist of CCR5 with potent anti-HIV activity, binds to a cavity formed between helices located near the extracellular surface of the receptor, which is different from the extracellular loop known as the ligand binding site.
A similar strategy aimed at identifying small molecule inhibitors of DARC, especially the extracellular N-terminal region bound by DBP, will be greatly useful in preventing P. In the absence of a continuous culture system for P.
Novel small molecule inhibitors of DARC such as monoclonal antibodies, soluble receptors, or variant versions of the protein, specifically targeting the DARC binding pocket, can be exploited. This could serve as potential effective strategy for antimalarial therapy either alone or in combination with existing antimalarial drugs to develop new drugs to block DBP—DARC interaction, thereby preventing reticulocyte invasion and consequently P.
In Grande Comore also known as Ngazidja the frequency of the Fy a- b- phenotype is 0. In Iran the Fy a-b- phenotype was found in 3. Recent work has identified a number of additional roles for this protein.
Asthma[ edit ] Asthma is more common and tends to be more severe in those of African descent. There appears to be a correlation with both total IgE levels and asthma and mutations in the Duffy antigen. The absence of erythroid DARC alters hematopoiesis including stem and progenitor cells, which ultimately gives rise to phenotypically distinct neutrophils.
This condition is associated with a reduced capacity to mobilize bone marrow neutrophil reserves in response to corticosteroids, despite normal cellularity and maturation of all cell lines in bone marrow aspirates. Strongly suggestive evidence has been found that links condition to a mutation in the Duffy gene. However once established, the absence of the DARC receptor appears to slow down the progression of the disease.
Leukopenia a low total white cell count is associated with relatively poor survival in HIV infection and this association is more marked in caucasians than in people of Black African descentdespite the on average lower white cell counts found in black Africans. The strength of this association increases inversely with the total white cell count.