TYMSTR, A PUTATIVE CHEMOKINE RECEPTOR SELECTIVELY EXPRESSED IN ACTIVATED T-CELLS, EXHIBITS HIV-1 CORECEPTOR FUNCTION

Background: Chemokines bind to specific receptors and mediate leukocyt e migration to sites of inflammation, Recently, some chemokine recepto rs, notably CXCR4 and CCR5, have been shown to be essential fusion fac tors on target cells for infection by human immunodeficiency virus (HI V); the chemokines bound by these receptors have also been shown to ac t as potent inhibitors of HIV infection, Here, we describe the isolati on of a novel, putative chemokine receptor, Results: We have isolated the cDNA for a putative human chemokine receptor, which we have termed TYMSTR (T-lymphocyte-expressed seven-transmembrane domain receptor), The TYMSTR gene is localized to human chromosome 3 and encodes a prote in thai has a high level of identity with chemokine receptors. TYMSTR mRNA was selectively expressed in interleukin-2-stimulated T lymphocyt es but not in freshly isolated lymphocytes and leukocytes or related c ell lines, The natural ligand for TYMSTR was Rot identified among 32 h uman chemokines and other potential ligands, Cells coexpressing TYMSTR and human CD4 fused with cells expressing envelope glycoproteins of m acrophage (M)-tropic HIV-1 as well as T-cell line (T)-tropic HIV-1 iso lates, Addition of infectious, T-tropic HIV-I particles to TYMSTR/CD4- expressing cells resulted in viral entry and proviral DNA formation. C onclusions: Our findings demonstrate that TYMSTR, in combination with CD4, mediates HIV-I fusion and entry. The high-level expression of TYM STR in CD4(+) T lymphocytes and the selectivity of this receptor for T -tropic and M-tropic HIV-1 strains indicates that TYMSTR might functio n as HIV coreceptor at both early and late stages of infection.