Linkage of the CCR5Δ32 mutation with a functional polymorphism of CD45RA

Hua Xin Liao, David C. Montefiori, Dhavalkumar D. Patel, David M. Lee, William K Scott, Margaret A Pericak-Vance, Barton F. Haynes

Research output: Contribution to journalArticle

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Abstract

A 32-bp deletion in CCR5 (CCR5Δ32) confers to PBMC resistance to HIV-1 isolates that use CCR5 as a coreceptor. To study this mutation in T cell development, we have screened 571 human thymus tissues for the mutation. We identified 72 thymuses (12.6%) that were heterozygous and 2 (0.35%) that were homozygous for the CCR5Δ32 mutation. We found that thymocyte development was normal in both CCR5Δ32 heterozygous and homozygous thymuses. In 3% of thymuses we identified a functional polymorphism of CD45RA, in which cortical and medullary thymocytes failed to down-regulate the 200- and 220-kDa CD45RA isoforms during T cell development. Moreover, we found an association of this CD45 functional polymorphism in thymuses with the CCRSΔ32 mutation (p = 0.00258). In vitro HIV-1 infection assays with CCR5-using primary isolates demonstrated that thymocytes with the heterozygous CCR5Δ32 mutation produced less p24 than did CCR5 wild-type thymocytes. However, the functional CD45RA polymorphism did not alter the susceptibility of thymocytes to HIV-1 infection. Taken together, these data demonstrate association of the CCR5A32 mutation with a polymorphism in an as yet unknown gene that is responsible for the ability to down-regulate the expression of high m.w. CD45RA isoforms. Although the presence of the CCR5Δ32 mutation down-regulates HIV-1 infection of thymocytes, the functional CD45RA polymorphism does not alter the susceptibility of thymocytes to HIV-1 infection in vitro.

Original languageEnglish
Pages (from-to)148-157
Number of pages10
JournalJournal of Immunology
Volume165
Issue number1
StatePublished - Jul 1 2000
Externally publishedYes

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Thymocytes
Thymus Gland
HIV-1
Mutation
HIV Infections
Down-Regulation
Protein Isoforms
T-Lymphocytes
Genes

ASJC Scopus subject areas

  • Immunology

Cite this

Liao, H. X., Montefiori, D. C., Patel, D. D., Lee, D. M., Scott, W. K., Pericak-Vance, M. A., & Haynes, B. F. (2000). Linkage of the CCR5Δ32 mutation with a functional polymorphism of CD45RA. Journal of Immunology, 165(1), 148-157.

Linkage of the CCR5Δ32 mutation with a functional polymorphism of CD45RA. / Liao, Hua Xin; Montefiori, David C.; Patel, Dhavalkumar D.; Lee, David M.; Scott, William K; Pericak-Vance, Margaret A; Haynes, Barton F.

In: Journal of Immunology, Vol. 165, No. 1, 01.07.2000, p. 148-157.

Research output: Contribution to journalArticle

Liao, HX, Montefiori, DC, Patel, DD, Lee, DM, Scott, WK, Pericak-Vance, MA & Haynes, BF 2000, 'Linkage of the CCR5Δ32 mutation with a functional polymorphism of CD45RA', Journal of Immunology, vol. 165, no. 1, pp. 148-157.
Liao, Hua Xin ; Montefiori, David C. ; Patel, Dhavalkumar D. ; Lee, David M. ; Scott, William K ; Pericak-Vance, Margaret A ; Haynes, Barton F. / Linkage of the CCR5Δ32 mutation with a functional polymorphism of CD45RA. In: Journal of Immunology. 2000 ; Vol. 165, No. 1. pp. 148-157.
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