Control of HIV-1 viremia and protection from AIDS are associated with HLA-Bw4 homozygosity.
Certain HLA-B antigens have been associated with lack of progression to AIDS. HLA-B alleles can be divided into two mutually exclusive groups based on the expression of the molecular epitopes HLA-Bw4 and HLA-Bw6. Notably, in addition to its role in presenting viral peptides for immune recognition, the HLA-Bw4, but not HLA-Bw6, motif functions as a ligand for a natural killer cell inhibitory receptor (KIR). Here, we show that profound suppression of HIV-1 viremia is significantly associated with homozygosity for HLA-B alleles that share the HLA-Bw4 epitope. Furthermore, homozygosity for HLA-Bw4 alleles was also significantly associated with the ability to remain AIDS free and to maintain a normal CD4 T cell count in a second cohort of HIV-1-infected individuals with well defined dates of seroconversion. This association was independent of the presence of a mutation in CC chemokine receptor 5 (CCR5) associated with resistance to HIV-1 infection, and it was independent of the presence of HLA alleles that could potentially confound the results. We conclude that homozygosity for HLA-Bw4-bearing B alleles is associated with a significant advantage and that the HLA-Bw4 motif is important in AIDS pathogenesis.
Flores-Villanueva
P O
PO
Dana-Farber Cancer Institute, One Jimmy Fund Way, Boston, MA 02115, USA.
Yunis
E J
EJ
Delgado
J C
JC
Vittinghoff
E
E
Buchbinder
S
S
Leung
J Y
JY
Uglialoro
A M
AM
Clavijo
O P
OP
Rosenberg
E S
ES
Kalams
S A
SA
Braun
J D
JD
Boswell
S L
SL
Walker
B D
BD
Goldfeld
A E
AE
D000163:Acquired Immunodeficiency Syndrome / Q000235:genetics* / Q000276:immunology* / Q000821:virology; D000328:Adult; D000483:Alleles; D018791:CD4 Lymphocyte Count; D015331:Cohort Studies; D018450:Disease Progression; D000939:Epitopes / Q000276:immunology; D005260:Female; D005787:Gene Frequency; D006679:HIV Seropositivity / Q000235:genetics / Q000276:immunology / Q000821:virology; D015497:HIV-1 / Q000276:immunology* / Q000502:physiology; D015235:HLA-B Antigens / Q000235:genetics* / Q000276:immunology*; D015236:HLA-C Antigens / Q000235:genetics / Q000276:immunology; D006720:Homozygote; D006801:Humans; D007694:Killer Cells, Natural / Q000276:immunology; D008297:Male; D008875:Middle Aged; D009154:Mutation / Q000235:genetics; D019713:Receptors, CCR5 / Q000235:genetics; D011971:Receptors, Immunologic / Q000276:immunology; D054340:Receptors, KIR; D013997:Time Factors; D019562:Viral Load; D014766:Viremia / Q000235:genetics / Q000276:immunology* / Q000821:virology
D000939:Epitopes; D015235:HLA-B Antigens; C042388:HLA-Bw4 antigen; D015236:HLA-C Antigens; D019713:Receptors, CCR5; D011971:Receptors, Immunologic; D054340:Receptors, KIR