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 language | English |
|---|---|
| Pages (from-to) | 148-157 |
| Number of pages | 10 |
| Journal | Journal of Immunology |
| Volume | 165 |
| Issue number | 1 |
| State | Published - Jul 1 2000 |
| Externally published | Yes |
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ASJC Scopus subject areas
- Immunology
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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 journal › Article
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TY - JOUR
T1 - Linkage of the CCR5Δ32 mutation with a functional polymorphism of CD45RA
AU - Liao, Hua Xin
AU - Montefiori, David C.
AU - Patel, Dhavalkumar D.
AU - Lee, David M.
AU - Scott, William K
AU - Pericak-Vance, Margaret A
AU - Haynes, Barton F.
PY - 2000/7/1
Y1 - 2000/7/1
N2 - 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.
AB - 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.
UR - http://www.scopus.com/inward/record.url?scp=0034235244&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=0034235244&partnerID=8YFLogxK
M3 - Article
C2 - 10861047
AN - SCOPUS:0034235244
VL - 165
SP - 148
EP - 157
JO - Journal of Immunology
JF - Journal of Immunology
SN - 0022-1767
IS - 1
ER -