Association between a defective CCR-5 gene and progression to disease in HIV infection.
We measured the effect(s) of CCR-5 genotype on disease progression by studying the frequency of a defective CCR-5 delta32 allele within a cohort of long-term infected individuals. An elevated frequency of CCR-5 delta32 heterozygotes within the cohort compared with a control population of blood donors was observed. An association between progression rate and CCR-5 delta32 heterozygosity was observed. Furthermore, analysis of proviral DNA V3 sequences from a subset of the cohort predicted that the majority of individuals (39 of 44) were infected with viruses predicted to utilize the beta-chemokine receptor CCR-5. The marked association between CCR-5 genotype and disease progression observed in this study may be a consequence of the predicted low frequency of CXCR-4-utilizing viruses present within the selected cohort.
Balfe
P
P
Department of Virology, UCLMS, London, UK. p.balfe@ucl.ac.uk
Churcher
Y
Y
Penny
M
M
Easterbrook
P J
PJ
Goodall
R L
RL
Galpin
S
S
Gotch
F
F
Daniels
R S
RS
McKeating
J A
JA
D000483:Alleles; D000595:Amino Acid Sequence; D018925:Chemokines / Q000097:blood; D015331:Cohort Studies; D016384:Consensus Sequence; D018450:Disease Progression; D015483:HIV Antibodies / Q000097:blood; D015699:HIV Envelope Protein gp120 / Q000235:genetics; D019302:HIV Envelope Protein gp160 / Q000235:genetics; D015658:HIV Infections / Q000235:genetics* / Q000276:immunology / Q000503:physiopathology*; D020276:HIV Long-Term Survivors; D015497:HIV-1; D006579:Heterozygote; D006801:Humans; D008969:Molecular Sequence Data; D010446:Peptide Fragments / Q000235:genetics; D019713:Receptors, CCR5 / Q000235:genetics* / Q000276:immunology; D013997:Time Factors
D018925:Chemokines; D015483:HIV Antibodies; D015699:HIV Envelope Protein gp120; D019302:HIV Envelope Protein gp160; C059762:HIV envelope protein gp120 (305-321); D010446:Peptide Fragments; D019713:Receptors, CCR5