title: Decreased NK cell frequency and function is associated with increased risk of KIR3DL allele polymorphism in simian immunodeficiency virus-infected rhesus macaques with high viral loads.
abstract: NK cells have been established as an important effector of innate immunity in a variety of viral infections. In HIV-1 infection in humans, alterations of NK cell function, frequency, and expression of various NK receptors have been reported to be associated with differential dynamics of disease progression. Expression of certain alleles of KIR3DL and KIR3DS receptors on NK cells was shown to correlate with levels of virus replication. In the SIV-infected rhesus macaque (RM) model of AIDS, several families of killer inhibitory Ig-related receptors (KIR receptors) corresponding to their human counterparts have been characterized, but only at the level of individual sequence variants. Here we define 14 different alleles of KIR3DL expressed among 38 SIV-infected RM, characterized by either high or low levels of SIV replication, by analyzing multiple sequences from individual animals and show an unequal distribution of certain alleles in these cohorts. High levels of SIV replication were associated with significant increases in KIR3DL mRNA levels in addition to decreases in both the frequency and function of NK cells in these animals. The higher frequency of inheritance of two KIR3DL alleles characterized by a single nucleotide polymorphism 159 H/Q was associated with RM that exhibited high plasma viral load. This data for the first time defines multiple alleles of KIR3DL in RM and shows an association between virus control, NK cell function and genetic polymorphisms of KIR receptors.
authors.affiliation: Department of Pathology and Laboratory Medicine, Emory University, Atlanta, GA 30322, USA. Pavel.Bostik@emory.edu
authors.forename: Pavel
authors.initials: P
authors.lastname: Bostik
authors.forename: Jaruda
authors.initials: J
authors.lastname: Kobkitjaroen
authors.forename: Weining
authors.initials: W
authors.lastname: Tang
authors.forename: Francois
authors.initials: F
authors.lastname: Villinger
authors.forename: Lara E
authors.initials: LE
authors.lastname: Pereira
authors.forename: Dawn M
authors.initials: DM
authors.lastname: Little
authors.forename: Susan T
authors.initials: ST
authors.lastname: Stephenson
authors.forename: Mark
authors.initials: M
authors.lastname: Bouzyk
authors.forename: Aftab A
authors.initials: AA
authors.lastname: Ansari
mesh_terms: D000483:Alleles; D000595:Amino Acid Sequence; D000818:Animals; D002999:Clone Cells; D015331:Cohort Studies; D020022:Genetic Predisposition to Disease; D006801:Humans; D020014:K562 Cells; D007694:Killer Cells, Natural / Q000276:immunology* / Q000473:pathology* / Q000821:virology; D018655:Lymphocyte Count; D008253:Macaca mulatta; D008969:Molecular Sequence Data; D020641:Polymorphism, Single Nucleotide / Q000235:genetics*; D054341:Receptors, KIR3DL1 / Q000235:genetics*; D012307:Risk Factors; D016097:Simian Acquired Immunodeficiency Syndrome / Q000235:genetics / Q000276:immunology* / Q000473:pathology / Q000821:virology; D015302:Simian Immunodeficiency Virus / Q000254:growth & development / Q000276:immunology*; D019562:Viral Load; D014779:Virus Replication / Q000276:immunology
chemical_list: D054341:Receptors, KIR3DL1