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Homozygous 32 deletion of the CCR5 chemokine receptor gene in an HIV1infected patient

Balotta, Claudia1,5; Bagnarelli, Patrizia2; Violin, Michela1; Ridolfo, Anna Lisa1; Zhou, Dan1; Berlusconi, Alberto1; Corvasce, Stefano1; Corbellino, Mario1; Clementi, Massimo3; Clerici, Mario4; Moroni, Mauro1; Galli, Massimo1

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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 Δ32/Δ32 homozygous individuals are protected against infection.

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

Design and 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/Δ32 heterozygous and Δ32/Δ32 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 Δ32/Δ32 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: Δ32/Δ32 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.

1Clinica delle Malattie Infettive, Università di Milano, Ospedale Luigi Sacco, Milan, Italy

2Istituto di Microbiologia, Università di Ancona, Ancona, Italy

3Dipartimento di Scienze Biomediche, Università di Trieste, Trieste, Italy

4Cattedra di Immunologia, Università di Milano, Padiglione LITA, Ospedale Luigi Sacco, Milan, Italy.

5Requests for reprints to: Dr Claudia Balotta, Clinica delle Malattie Infettive, Università di Milano, Ospedale Luigi Sacco, Via G.B. Grassi 74, 20157 Milano, Italy.

Sponsorship: This work was supported by grants from Istituto Superiore di Sanità, IX Progetto AIDS no. 9404-78 (C.B.), no. 9304-39 (M. Clementi), no. 9304-34 (M. Clerici), no. 9402-10 (M.G.) and no. 9403-78 (M.M.).

Date of receipt: 28 April 1997; accepted: 22 May 1997.

© Lippincott-Raven Publishers.