HIV-1 Tat protein mimicry of chemokines

The HIV-1 Tat protein is a potent chemoattractant for monocytes. We observed that Tat shows conserved amino acids corresponding to critical sequences of the chemokines, a family of molecules known for their potent ability to attract monocytes. Synthetic Tat and a peptide ([CysL.sub.24-51]) encompassing the 'chemokine-like' region of Tat induced a rapid and transient [Ca.sup.2+] influx in monocytes and macrophages, analogous to [Beta]-chemokines. Both monocyte migration and [Ca.sup.2+] mobilization were pertussis toxin sensitive and cholera toxin insensitive. Cross-desensitization studies indicated that Tat shares receptors with MCP-1, MCP-3, and eotaxin. Tat was able to displace binding of [Beta]-chemokines from the [Beta]-chemokine receptors CCR2 and CCR3, but not CCR1, CCR4, and CCR5. Direct receptor binding experiments with the [CysL.sub.24-51] peptide confirmed binding to cells transfected with CCR2 and CCR3. HIV-1 Tat appears to mimic [Beta]-chemokine features, which may serve to locally recruit chemokine receptor-expressing monocytes/macrophages toward HIV producing cells and facilitate activation and infection.