Abstract

Introduction: The CC chemokine receptor 5 (CCR5) is known as the main co-receptor in human immunodeficiency virus (HIV) infection. Accumulating evidence verified 32bp deletion in both alleles of CCR5 provides natural resistance to HIV infection. Accordingly, recent therapeutic approaches are based on gene and cell therapies by inducing this resistance. Allogeneic transplantation of stem cells with CCR5Δ32 homozygous to HIV infected people has been considered as an efficient strategy. Objectives: The aim of this study was to determine CCR5 Δ32 mutation frequency in healthy and HIV-infected individuals in Zanjan province, in Iran and also detecting appropriate candidate for future therapeutic approaches. Patients and Methods: In this study, blood samples were collected from 102 HIV infected patients and 204 healthy controls in ethylene diamine tetra-acetic acid (EDTA) pre-coated tubes. DNA extraction was performed and analyzed for CCR5Δ32 mutation by GAP-PCR in both groups and followed by 2% gel agarose electrophoresis. The Δ32 genotype frequency was statistically determined. Results: Our finding demonstrated that 3 HIV infected patients displayed CCR5 mutation, while 204 healthy controls showed one CCR5 Δ32/Δ32 homozygote mutation. We observed that Δ32 mutation frequency is 0.82% in Zanjan province (χ2 =47.58, P<0.001). Conclusion: Reduction in CCR5 mutation frequency as well as the other polymorphisms related to HIV resistance, can lead to the development of HIV infection epidemiology. Migration, natural selection and genetic admixture can elucidate various distribution of Δ32 allele frequency in different populations, like as north Europeans that reduce gradually to south. The result of this study can facilitate the presentation of suitable Δ32 donors to HIV infected patients in therapeutic approaches.

Highlights

  • The CC chemokine receptor 5 (CCR5) is known as the main co-receptor in human immunodeficiency virus (HIV) infection

  • In a study on 102 HIV-infected patients, we found reduction in CCR5 mutation frequency as well as the other polymorphisms related to HIV resistance, can lead to the development of HIV infection

  • This study was performed on 102 HIV+ and 204 healthy samples in Zanjan province in Iran

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Summary

Introduction

The CC chemokine receptor 5 (CCR5) is known as the main co-receptor in human immunodeficiency virus (HIV) infection. Recent therapeutic approaches are based on gene and cell therapies by inducing this resistance. Objectives: The aim of this study was to determine CCR5 Δ32 mutation frequency in healthy and HIV-infected individuals in Zanjan province, in Iran and detecting appropriate candidate for future therapeutic approaches. Conclusion: Reduction in CCR5 mutation frequency as well as the other polymorphisms related to HIV resistance, can lead to the development of HIV infection epidemiology. After viral entry into the host immune cells, external virus glycoprotein (gp120) binds to CD4+ receptor and provides conformational change in gp that leads to interaction with the coreceptors (Cc-chemokine receptor-5: CCR5 or CXCR4). It has been demonstrated that 32bp deletion in both alleles of CCR5 inhibits HIV entry into the CD4+ T cells, macrophages and provided “natural resistance” to HIV [1, 2].

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