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R5 HIV gp120-mediated cellular contacts induce the death of single CCR5-expressing CD4 T cells by a gp41-dependent mechanism
Ist Teil von
Journal of leukocyte biology, 2004-10, Vol.76 (4), p.804-811
Ort / Verlag
United States: Society for Leukocyte Biology
Erscheinungsjahr
2004
Link zum Volltext
Quelle
Wiley Online Library - AutoHoldings Journals
Beschreibungen/Notizen
The use of CXC chemokine receptor 4 (CXCR4) and CC chemokine receptor 5 (CCR5) by X4 and R5 human immunodeficiency virus (HIV) envelopes (Env) influences HIV cytopathicity. Here, we have evaluated the role of CCR5 and gp41 in Env‐induced cell death occurring during the contacts of uninfected, primary cells with MOLT cells infected with different R5 and X4 HIV isolates. As reported for X4‐Env, R5 HIV‐infected cells destroyed CD4 T cells expressing the appropriate coreceptor by inducing the formation of syncytia and the death of single target cells. Therefore, only the small (<10%) CCR5+ subset of primary CD4 T cells was sensitive to cellular presentation of R5‐Env, and CCR5–CD4 T cells showed complete resistance to R5‐Env‐mediated cell death. X4‐ and R5‐infected cells killed single primary cells by a common mechanism that was dependent on gp41 function and induced a rapid loss of mitochondrial membrane potential and plasma membrane integrity in target cells. Single‐cell death was not affected by the blockade of HIV replication in target cells or G‐protein signaling through CXCR4/CCR5. In contrast, caspase inhibition (Z‐Val‐Ala‐Asp‐fluoromethylketone) profoundly changed the outcome of cell‐to‐cell contacts by reducing the number of single dead CD4 T cells and increasing the rate of syncytium formation. In conclusion, X4 and R5 HIV Env share a common gp41‐dependent mechanism to kill CD4 T cells during cellular contacts. Env tropism and coreceptor expression but not differential killing mechanisms seem to govern the extent of cytopathic effects induced by HIV infection.