Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
6
pubmed:dateCreated
1998-10-6
pubmed:abstractText
Thymocyte infection with HIV-1 is associated with thymic involution and impaired thymopoiesis, particularly in pediatric patients. To define mechanisms of thymocyte infection, we examined human thymocytes for expression and function of CXCR4 and CCR5, the major cell entry coreceptors for T cell line-tropic (T-tropic) and macrophage-tropic (M-tropic) strains of HIV-1, respectively. CXCR4 was detected on the surface of all thymocytes. CXCR4 expression on mature, high level TCR thymocytes was similar to that on peripheral blood T cells, but was much lower than that on immature thymocytes, including CD34+ thymic progenitors. Consistent with this, stroma-derived factor-1 (SDF-1) induced calcium flux primarily in immature thymocytes, with CD34+ progenitors giving the strongest response. In addition, SDF-1 mRNA was detected in thymic-derived stromal cells, and SDF-1 induced chemotaxis of thymocytes, suggesting that CXCR4 may play a role in thymocyte migration. Infection of immature thymocytes by the T-tropic HIV-1 strain LAI was 10-fold more efficient than that in mature thymocytes, consistent with their relative CXCR4 surface expression. Anti-CXCR4 antiserum or SDF-1 blocked fusion of thymocytes with cells expressing the LAI envelope. In contrast to CXCR4, CCR5 was detected at low levels on thymocytes, and CCR5 agonists did not induce calcium flux or chemotaxis in thymocytes. However, CD4+ mature thymocytes were productively infected with the CCR5-tropic strain Ba-L, and this infection was specifically inhibited with the CCR5 agonist, macrophage inflammatory protein-1beta. Our data provide strong evidence that CXCR4 and CCR5 function as coreceptors for HIV-1 infection of human thymocytes.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
AIM
pubmed:chemical
http://linkedlifedata.com/resource/pubmed/chemical/Antigens, CD34, http://linkedlifedata.com/resource/pubmed/chemical/CXCL12 protein, human, http://linkedlifedata.com/resource/pubmed/chemical/Calcium, http://linkedlifedata.com/resource/pubmed/chemical/Chemokine CXCL12, http://linkedlifedata.com/resource/pubmed/chemical/Chemokines, CC, http://linkedlifedata.com/resource/pubmed/chemical/Chemokines, CXC, http://linkedlifedata.com/resource/pubmed/chemical/DNA, Viral, http://linkedlifedata.com/resource/pubmed/chemical/Gene Products, env, http://linkedlifedata.com/resource/pubmed/chemical/RNA, Messenger, http://linkedlifedata.com/resource/pubmed/chemical/Receptors, CCR5, http://linkedlifedata.com/resource/pubmed/chemical/Receptors, CXCR4, http://linkedlifedata.com/resource/pubmed/chemical/Receptors, HIV
pubmed:status
MEDLINE
pubmed:month
Sep
pubmed:issn
0022-1767
pubmed:author
pubmed:issnType
Print
pubmed:day
15
pubmed:volume
161
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
3103-13
pubmed:dateRevised
2007-11-15
pubmed:meshHeading
pubmed-meshheading:9743377-Antigens, CD34, pubmed-meshheading:9743377-Calcium, pubmed-meshheading:9743377-Cell Differentiation, pubmed-meshheading:9743377-Cell Fusion, pubmed-meshheading:9743377-Cell Movement, pubmed-meshheading:9743377-Cells, Cultured, pubmed-meshheading:9743377-Chemokine CXCL12, pubmed-meshheading:9743377-Chemokines, CC, pubmed-meshheading:9743377-Chemokines, CXC, pubmed-meshheading:9743377-Child, Preschool, pubmed-meshheading:9743377-DNA, Viral, pubmed-meshheading:9743377-Fetal Blood, pubmed-meshheading:9743377-Gene Products, env, pubmed-meshheading:9743377-HIV Infections, pubmed-meshheading:9743377-HIV-1, pubmed-meshheading:9743377-Hematopoietic Stem Cells, pubmed-meshheading:9743377-Humans, pubmed-meshheading:9743377-Infant, pubmed-meshheading:9743377-Proviruses, pubmed-meshheading:9743377-RNA, Messenger, pubmed-meshheading:9743377-Receptors, CCR5, pubmed-meshheading:9743377-Receptors, CXCR4, pubmed-meshheading:9743377-Receptors, HIV, pubmed-meshheading:9743377-Stromal Cells, pubmed-meshheading:9743377-T-Lymphocyte Subsets, pubmed-meshheading:9743377-Thymus Gland
pubmed:year
1998
pubmed:articleTitle
CXCR4 and CCR5 on human thymocytes: biological function and role in HIV-1 infection.
pubmed:affiliation
Division of Viral Products, Center for Biologics Evaluation and Research, Food and Drug Administration, National Institutes of Health, Bethesda, MD 20892, USA.
pubmed:publicationType
Journal Article, Research Support, U.S. Gov't, P.H.S.