title: Founder effects in the assessment of HIV polymorphisms and HLA allele associations.
abstract: Escape from T cell-mediated immune responses affects the ongoing evolution of rapidly evolving viruses such as HIV. By applying statistical approaches that account for phylogenetic relationships among viral sequences, we show that viral lineage effects rather than immune escape often explain apparent human leukocyte antigen (HLA)-mediated immune-escape mutations defined by older analysis methods. Phylogenetically informed methods identified immune-susceptible locations with greatly improved accuracy, and the associations we identified with these methods were experimentally validated. This approach has practical implications for understanding the impact of host immunity on pathogen evolution and for defining relevant variants for inclusion in vaccine antigens.
authors.affiliation: Los Alamos National Laboratory, Los Alamos, NM 87545, USA.
authors.forename: Tanmoy
authors.initials: T
authors.lastname: Bhattacharya
authors.forename: Marcus
authors.initials: M
authors.lastname: Daniels
authors.forename: David
authors.initials: D
authors.lastname: Heckerman
authors.forename: Brian
authors.initials: B
authors.lastname: Foley
authors.forename: Nicole
authors.initials: N
authors.lastname: Frahm
authors.forename: Carl
authors.initials: C
authors.lastname: Kadie
authors.forename: Jonathan
authors.initials: J
authors.lastname: Carlson
authors.forename: Karina
authors.initials: K
authors.lastname: Yusim
authors.forename: Ben
authors.initials: B
authors.lastname: McMahon
authors.forename: Brian
authors.initials: B
authors.lastname: Gaschen
authors.forename: Simon
authors.initials: S
authors.lastname: Mallal
authors.forename: James I
authors.initials: JI
authors.lastname: Mullins
authors.forename: David C
authors.initials: DC
authors.lastname: Nickle
authors.forename: Joshua
authors.initials: J
authors.lastname: Herbeck
authors.forename: Christine
authors.initials: C
authors.lastname: Rousseau
authors.forename: Gerald H
authors.initials: GH
authors.lastname: Learn
authors.forename: Toshiyuki
authors.initials: T
authors.lastname: Miura
authors.forename: Christian
authors.initials: C
authors.lastname: Brander
authors.forename: Bruce
authors.initials: B
authors.lastname: Walker
authors.forename: Bette
authors.initials: B
authors.lastname: Korber
mesh_terms: D000483:Alleles; D017951:Antigen Presentation; D000939:Epitopes; D019143:Evolution, Molecular; D018703:Founder Effect; D005805:Genes, MHC Class I; D005814:Genes, Viral; D015658:HIV Infections / Q000276:immunology / Q000821:virology*; D015497:HIV-1 / Q000145:classification / Q000235:genetics* / Q000276:immunology*; D006680:HLA Antigens / Q000235:genetics* / Q000276:immunology; D015236:HLA-C Antigens / Q000235:genetics; D006801:Humans; D007108:Immune Tolerance; D016013:Likelihood Functions; D009154:Mutation; D010641:Phenotype; D010802:Phylogeny; D011110:Polymorphism, Genetic; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology
chemical_list: D000939:Epitopes; D006680:HLA Antigens; D015236:HLA-C Antigens