title: A homologous naturally occurring mutation in Duffy and CCR5 leading to reduced receptor expression.
abstract: Genetic variations in the CC chemokine receptor (CCR5) leading to reduced or absent expression are associated with resistance to human immunodeficiency virus infection and delayed onset of acquired immunodeficiency syndrome. Similarly, lack of the red-cell chemokine receptor Duffy confers protection against malarial infection by Plasmodium vivax. Investigators have previously described a missense mutation (R89C) in the first intracellular loop of Duffy that results in reduced protein expression. The present study shows that the lower Duffy expression is due to loss of the positive charge at this position, resulting in protein instability. Moreover, R60S, a mutation in the first intracellular loop of CCR5 noted in a recent cohort study, likewise results in reduced surface expression and function of CCR5. The presence of a homologous, naturally occurring mutation that may be protective against disease thus defines a novel mechanism accounting for the decreased expression of these receptors in some individuals. (Blood. 2001;97:3651-3654)
authors.affiliation: Immunochemistry Laboratory, New York Blood Center, 310 East 67th St., New York, NY 10021, USA.
authors.forename: D
authors.initials: D
authors.lastname: Tamasauskas
authors.forename: V
authors.initials: V
authors.lastname: Powell
authors.forename: K
authors.initials: K
authors.lastname: Saksela
authors.forename: K
authors.initials: K
authors.lastname: Yazdanbakhsh
mesh_terms: D000953:Antigens, Protozoan; D002118:Calcium / Q000378:metabolism; D002352:Carrier Proteins / Q000235:genetics* / Q000502:physiology; D002460:Cell Line; D004375:Duffy Blood-Group System / Q000235:genetics* / Q000502:physiology; D015870:Gene Expression; D015497:HIV-1 / Q000502:physiology; D006801:Humans; D015151:Immunoblotting; D008288:Malaria / Q000517:prevention & control; D016297:Mutagenesis, Site-Directed; D009154:Mutation; D015800:Protozoan Proteins; D019713:Receptors, CCR5 / Q000235:genetics* / Q000502:physiology; D011956:Receptors, Cell Surface / Q000235:genetics* / Q000502:physiology; D014162:Transfection
chemical_list: D000953:Antigens, Protozoan; D002352:Carrier Proteins; D004375:Duffy Blood-Group System; C066001:Duffy antigen binding protein, Plasmodium; D015800:Protozoan Proteins; D019713:Receptors, CCR5; D011956:Receptors, Cell Surface; D002118:Calcium