Homozygous delta 32 deletion of the CCR-5 chemokine receptor gene in an HIV-1-infected patient.
BACKGROUND
Recent research has found that entry of non-syncytium-inducing (NSI), monocyte-macrophage-tropic HIV-1 isolates requires binding to both CD4 and CCR5 receptors, and that delta 32/delta 32 homozygous individuals are protected against infection.


OBJECTIVE
To analyse the polymorphism of CCR-5 gene in HIV-1-infected and uninfected subjects.


METHODS
CCR-5 sequences were amplified by polymerase chain reaction (PCR) from DNA of peripheral blood mononuclear cells. Samples from 152 HIV-1-infected subjects and 122 uninfected controls were tested for the detection of the 32 base-pair deletion. HIV-1 phenotype was determined by viral isolation and MT-2 evaluation.


RESULTS
The wild-type/delta 32 heterozygous and delta 32/delta 32 homozygous conditions were represented in 10.7 and 0.8% of healthy controls and in 9.8 and 0.7% of HIV-1-infected subjects, respectively. Of note, the delta 32/delta 32 deletion of the CCR-5 gene was detected by PCR and sequencing confirmed in a patient with progressive infection harbouring a clade B virus with SI phenotype.


CONCLUSIONS
delta 32/delta 32 homozygosity for the CCR-5 gene does not confer absolute protection against HIV-1 infection, suggesting that either macrophage-tropic viral strains could use coreceptors other than CCR-5 or infect independently of the presence of a functional CCR-5 coreceptor. Alternatively, primary infection sustained by T-cell-tropic isolates, although exceptional, may occur.
Balotta
C
C
Clinica delle Malattie Infettive, Università di Milano, Ospedale Luigi Sacco, Italy.
Bagnarelli
P
P
Violin
M
M
Ridolfo
A L
AL
Zhou
D
D
Berlusconi
A
A
Corvasce
S
S
Corbellino
M
M
Clementi
M
M
Clerici
M
M
Moroni
M
M
Galli
M
M
D000328:Adult; D003001:Cloning, Molecular; D015331:Cohort Studies; D015699:HIV Envelope Protein gp120 / Q000235:genetics; D006679:HIV Seropositivity / Q000453:epidemiology / Q000235:genetics*; D015497:HIV-1 / Q000145:classification / Q000472:pathogenicity*; D006579:Heterozygote; D006801:Humans; D007113:Immunity, Innate / Q000235:genetics; D007558:Italy / Q000453:epidemiology; D008297:Male; D009154:Mutation; D016133:Polymerase Chain Reaction; D011110:Polymorphism, Genetic; D019713:Receptors, CCR5; D018121:Receptors, Cytokine / Q000235:genetics*; D015728:Receptors, HIV / Q000235:genetics*; D012307:Risk Factors; D017422:Sequence Analysis, DNA; D017384:Sequence Deletion; D014766:Viremia / Q000175:diagnosis; D044465:White People / Q000235:genetics
D015699:HIV Envelope Protein gp120; D019713:Receptors, CCR5; D018121:Receptors, Cytokine; D015728:Receptors, HIV