Heterozygosity for a defective gene for CC chemokine receptor 5 is not the sole determinant for the immunologic and virologic phenotype of HIV-infected long-term nonprogressors

Détails

ID Serval
serval:BIB_46BE7661B3AE
Type
Article: article d'un périodique ou d'un magazine.
Collection
Publications
Titre
Heterozygosity for a defective gene for CC chemokine receptor 5 is not the sole determinant for the immunologic and virologic phenotype of HIV-infected long-term nonprogressors
Périodique
Journal of Clinical Investigation
Auteur(s)
Cohen  O. J., Vaccarezza  M., Lam  G. K., Baird  B. F., Wildt  K., Murphy  P. M., Zimmerman  P. A., Nutman  T. B., Fox  C. H., Hoover  S., Adelsberger  J., Baseler  M., Arthos  J., Davey, R. T., Jr. , Dewar  R. L., Metcalf  J., Schwartzentruber  D. J., Orenstein  J. M., Buchbinder  S., Saah  A. J., Detels  R., Phair  J., Rinaldo  C., Margolick  J. B., Pantaleo  G., Fauci  A. S.
ISSN
0021-9738 (Print)
Statut éditorial
Publié
Date de publication
09/1997
Volume
100
Numéro
6
Pages
1581-9
Notes
Journal Article
Research Support, Non-U.S. Gov't
Research Support, U.S. Gov't, P.H.S. --- Old month value: Sep 15
Résumé
HIV-1-infected long-term nonprogressors are a heterogeneous group of individuals with regard to immunologic and virologic markers of HIV-1 disease. CC chemokine receptor 5 (CCR5) has recently been identified as an important coreceptor for HIV-1 entry into CD4+ T cells. A mutant allele of CCR5 confers a high degree of resistance to HIV-1 infection in homozygous individuals and partial protection against HIV disease progression in heterozygotes. The frequency of CCR5 heterozygotes is increased among HIV-1- infected long-term nonprogressors compared with progressors; however, the host defense mechanisms responsible for nonprogression in CCR5 heterozygotes are unknown. We hypothesized that nonprogressors who were heterozygous for the mutant CCR5 gene might define a subgroup of nonprogressors with higher CD4+ T cell counts and lower viral load compared with CCR5 wild-type nonprogressors. However, in a cohort of 33 HIV-1-infected long-term nonprogressors, those who were heterozygous for the mutant CCR5 gene were indistinguishable from CCR5 wild-type nonprogressors with regard to all measured immunologic and virologic parameters. Although epidemiologic data support a role for the mutant CCR5 allele in the determination of the state of long-term nonprogression in some HIV-1- infected individuals, it is not the only determinant. Furthermore, long-term nonprogressors with the wild-type CCR5 genotype are indistinguishable from heterozygotes from an immunologic and virologic standpoint.
Mots-clé
Adult CD4-Positive T-Lymphocytes/immunology Disease Progression Disease-Free Survival Female HIV Infections/*genetics/immunology/virology HIV-1/isolation & purification/*pathogenicity Heterozygote Homozygote Humans Immunohistochemistry In Situ Hybridization Lymph Nodes/chemistry/virology Macrophage Inflammatory Protein-1/blood Male Middle Aged Monocytes/immunology *Mutation RANTES/blood Receptors, CCR5/*genetics/metabolism Receptors, Complement 3d/analysis Viral Load
Pubmed
Web of science
Open Access
Oui
Création de la notice
25/01/2008 16:13
Dernière modification de la notice
08/05/2019 17:58
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