Linkage of the CCR5 Delta 32 mutation with a functional polymorphism of CD45RA.


Journal Article

A 32-bp deletion in CCR5 (CCR5 Delta 32) 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 CCR5 Delta 32 mutation. We found that thymocyte development was normal in both CCR5 Delta 32 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 CCR5 Delta 32 mutation (p = 0.00258). In vitro HIV-1 infection assays with CCR5-using primary isolates demonstrated that thymocytes with the heterozygous CCR5 Delta 32 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 CCR5 Delta 32 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 CCR5 Delta 32 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.

Full Text

Duke Authors

Cited Authors

  • Liao, HX; Montefiori, DC; Patel, DD; Lee, DM; Scott, WK; Pericak-Vance, M; Haynes, BF

Published Date

  • July 1, 2000

Published In

Volume / Issue

  • 165 / 1

Start / End Page

  • 148 - 157

PubMed ID

  • 10861047

Pubmed Central ID

  • 10861047

International Standard Serial Number (ISSN)

  • 0022-1767

Digital Object Identifier (DOI)

  • 10.4049/jimmunol.165.1.148


  • eng

Conference Location

  • United States