Analysis of CCR5, CCR2, SDF1 and RANTES gene polymorphisms in subjects with HIV-related PML and not determined leukoencephalopathy

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Abstract

Progressive Multifocal Leukoencephalopathy (PML) is a fatal demyelinating disease of the central nervous system (CNS) caused by JC virus (JCV), a human polyomavirus that can lytically infect and destroy the oligodendrocites in immunosuppressed individuals. After the introduction of highly active antiretroviral therapy (HAART) for AIDS treatment, a PML-like leukoencephalopathy, known as non-determined leukoencephalopathy (NDLE), has also been observed. Since a number of host genetic factors have been identified as having an impact on susceptibility to HIV-1 infection and in the progression to AIDS and death, in this work we analysed the pattern of distribution of different chemokine and chemokine receptor polymorphisms that seem to be involved in HIV+ neurological diseases. The CCR5, RANTES, CCR2 and SDF1 genes were molecularly analysed in 84 HIV+ HAART treated subjects: 55 without neurological disorders (HIV+), 12 HIV+ NDLE and 17 HIV+ PML patients. The RANTES -403 G/A polymorphism was significantly associated with NDLE. These data suggest that mutation of the RANTES allele can predispose to the induction of demyelination similarly to what has been observed in Multiple Sclerosis (MS) and may suggest a possible explanation for the development of leukoencephalopathy without detection of JCV.

Original languageEnglish
Pages (from-to)26-30
Number of pages5
JournalBiomedicine and Pharmacotherapy
Volume62
Issue number1
DOIs
Publication statusPublished - Jan 2008

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Progressive Multifocal Leukoencephalopathy
Leukoencephalopathies
Chemokine CCL5
HIV
JC Virus
Genes
Highly Active Antiretroviral Therapy
Demyelinating Diseases
Acquired Immunodeficiency Syndrome
Polyomavirus
Chemokine Receptors
Nervous System Diseases
Chemokines
Multiple Sclerosis
HIV Infections
HIV-1
Central Nervous System
Alleles
Mutation

Keywords

  • Chemokines
  • HIV
  • Progressive Multifocal Leukoencephalopathy
  • RANTES

ASJC Scopus subject areas

  • Pharmacology

Cite this

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title = "Analysis of CCR5, CCR2, SDF1 and RANTES gene polymorphisms in subjects with HIV-related PML and not determined leukoencephalopathy",
abstract = "Progressive Multifocal Leukoencephalopathy (PML) is a fatal demyelinating disease of the central nervous system (CNS) caused by JC virus (JCV), a human polyomavirus that can lytically infect and destroy the oligodendrocites in immunosuppressed individuals. After the introduction of highly active antiretroviral therapy (HAART) for AIDS treatment, a PML-like leukoencephalopathy, known as non-determined leukoencephalopathy (NDLE), has also been observed. Since a number of host genetic factors have been identified as having an impact on susceptibility to HIV-1 infection and in the progression to AIDS and death, in this work we analysed the pattern of distribution of different chemokine and chemokine receptor polymorphisms that seem to be involved in HIV+ neurological diseases. The CCR5, RANTES, CCR2 and SDF1 genes were molecularly analysed in 84 HIV+ HAART treated subjects: 55 without neurological disorders (HIV+), 12 HIV+ NDLE and 17 HIV+ PML patients. The RANTES -403 G/A polymorphism was significantly associated with NDLE. These data suggest that mutation of the RANTES allele can predispose to the induction of demyelination similarly to what has been observed in Multiple Sclerosis (MS) and may suggest a possible explanation for the development of leukoencephalopathy without detection of JCV.",
keywords = "Chemokines, HIV, Progressive Multifocal Leukoencephalopathy, RANTES",
author = "Guerini, {Franca R.} and Serena Delbue and Milena Zanzottera and Cristina Agliardi and Marina Saresella and Roberta Mancuso and Renato Maserati and Enrico Marchioni and Andrea Gori and Pasquale Ferrante",
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T1 - Analysis of CCR5, CCR2, SDF1 and RANTES gene polymorphisms in subjects with HIV-related PML and not determined leukoencephalopathy

AU - Guerini, Franca R.

AU - Delbue, Serena

AU - Zanzottera, Milena

AU - Agliardi, Cristina

AU - Saresella, Marina

AU - Mancuso, Roberta

AU - Maserati, Renato

AU - Marchioni, Enrico

AU - Gori, Andrea

AU - Ferrante, Pasquale

PY - 2008/1

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N2 - Progressive Multifocal Leukoencephalopathy (PML) is a fatal demyelinating disease of the central nervous system (CNS) caused by JC virus (JCV), a human polyomavirus that can lytically infect and destroy the oligodendrocites in immunosuppressed individuals. After the introduction of highly active antiretroviral therapy (HAART) for AIDS treatment, a PML-like leukoencephalopathy, known as non-determined leukoencephalopathy (NDLE), has also been observed. Since a number of host genetic factors have been identified as having an impact on susceptibility to HIV-1 infection and in the progression to AIDS and death, in this work we analysed the pattern of distribution of different chemokine and chemokine receptor polymorphisms that seem to be involved in HIV+ neurological diseases. The CCR5, RANTES, CCR2 and SDF1 genes were molecularly analysed in 84 HIV+ HAART treated subjects: 55 without neurological disorders (HIV+), 12 HIV+ NDLE and 17 HIV+ PML patients. The RANTES -403 G/A polymorphism was significantly associated with NDLE. These data suggest that mutation of the RANTES allele can predispose to the induction of demyelination similarly to what has been observed in Multiple Sclerosis (MS) and may suggest a possible explanation for the development of leukoencephalopathy without detection of JCV.

AB - Progressive Multifocal Leukoencephalopathy (PML) is a fatal demyelinating disease of the central nervous system (CNS) caused by JC virus (JCV), a human polyomavirus that can lytically infect and destroy the oligodendrocites in immunosuppressed individuals. After the introduction of highly active antiretroviral therapy (HAART) for AIDS treatment, a PML-like leukoencephalopathy, known as non-determined leukoencephalopathy (NDLE), has also been observed. Since a number of host genetic factors have been identified as having an impact on susceptibility to HIV-1 infection and in the progression to AIDS and death, in this work we analysed the pattern of distribution of different chemokine and chemokine receptor polymorphisms that seem to be involved in HIV+ neurological diseases. The CCR5, RANTES, CCR2 and SDF1 genes were molecularly analysed in 84 HIV+ HAART treated subjects: 55 without neurological disorders (HIV+), 12 HIV+ NDLE and 17 HIV+ PML patients. The RANTES -403 G/A polymorphism was significantly associated with NDLE. These data suggest that mutation of the RANTES allele can predispose to the induction of demyelination similarly to what has been observed in Multiple Sclerosis (MS) and may suggest a possible explanation for the development of leukoencephalopathy without detection of JCV.

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