Founder effects in the assessment of HIV polymorphisms and HLA allele associations.
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.
Bhattacharya
Tanmoy
T
Los Alamos National Laboratory, Los Alamos, NM 87545, USA.
Daniels
Marcus
M
Heckerman
David
D
Foley
Brian
B
Frahm
Nicole
N
Kadie
Carl
C
Carlson
Jonathan
J
Yusim
Karina
K
McMahon
Ben
B
Gaschen
Brian
B
Mallal
Simon
S
Mullins
James I
JI
Nickle
David C
DC
Herbeck
Joshua
J
Rousseau
Christine
C
Learn
Gerald H
GH
Miura
Toshiyuki
T
Brander
Christian
C
Walker
Bruce
B
Korber
Bette
B
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
D000939:Epitopes; D006680:HLA Antigens; D015236:HLA-C Antigens