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-indu cing (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 th e polymorphism of CCR-5 gene in HIV-1-infected and uninfected subjects . Design and methods: CCR-5 sequences were amplified by polymerase cha in reaction (PCR) from DNA of peripheral blood mononuclear cells. Samp les from 152 HIV-l-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 w ild-type/Delta 32 heterozygous and Delta 32/Delta 32 homozygous condit ions 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 sequenc ing confirmed in a patient with progressive infection harbouring a cla de B virus with SI phenotype. Conclusions: Delta 32/Delta 32 homozygos ity for the CCR-5 gene does not confer absolute protection against HIV -1 infection, suggesting that either macrophage-tropic viral strains c ould use coreceptors other than CCR-5 or infect independently of the p resence of a functional CCR-5 coreceptor. Alternatively, primary infec tion sustained by T-cell-tropic isolates, although exceptional, may oc cur.