Protection against parenteral HIV-1 infection by homozygous deletion in the C-C chemokine receptor 5 gene.
OBJECTIVE
To investigate the role of the CC chemokine receptor 5 (CCR5) for parenteral transmission of HIV-1.


METHODS
The prevalence of the delta32 deletion within the CCR5 gene was determined in a cohort of 207 patients, who had received documented amounts of non-antibody-tested and non-inactivated clotting factor concentrate.


METHODS
Chromosomal DNA of haemophiliacs was isolated from whole blood. A portion of the CCR5 gene spanning the delta32 deletion was amplified by PCR. The resulting DNA fragments were analysed by agarose gel electrophoresis.


RESULTS
The rate of HIV-1 infection was correlated strongly with increasing amounts of inoculated clotting factor concentrate. None of the HIV-positive patients (n = 129) had the delta32/delta32 genotype, whereas 12 out of 78 HIV-negative haemophiliacs had the homozygous delta32 deletion.


CONCLUSIONS
The delta32/delta32 genotype was highly protective against HIV-1 infection, even in patients who had received millions of non-inactivated clotting factor units. As it is likely that in the early 1980s plasma pools were contaminated not only with monocyte-tropic HIV-1 strains, CCR5 appears to be the major mediator of HIV-1 infection. Furthermore, we conclude that there must be other protective mechanisms in multiply exposed non-infected haemophiliacs who have wild-type CCR5.
Kupfer
B
B
Institute of Medical Microbiology and Immunology, University of Bonn, Germany.
Kaiser
R
R
Brackmann
H H
HH
Effenberger
W
W
Rockstroh
J K
JK
Matz
B
B
Schneweis
K E
KE
D001483:Base Sequence; D018791:CD4 Lymphocyte Count; D015331:Cohort Studies; D004247:DNA / Q000032:analysis; D005838:Genotype; D015658:HIV Infections / Q000150:complications / Q000276:immunology* / Q000635:transmission*; D015497:HIV-1 / Q000502:physiology*; D006467:Hemophilia A / Q000150:complications* / Q000235:genetics; D006801:Humans; D012367:RNA, Viral / Q000097:blood; D019713:Receptors, CCR5 / Q000235:genetics*; D017384:Sequence Deletion
D012367:RNA, Viral; D019713:Receptors, CCR5; D004247:DNA