title: HIV-1 Tat protein mimicry of chemokines.
abstract: 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 (CysL24-51) encompassing the "chemokine-like" region of Tat induced a rapid and transient Ca2+ influx in monocytes and macrophages, analogous to beta-chemokines. Both monocyte migration and Ca2+ 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 CysL24-51 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.
authors.affiliation: Centro di Biotecnologie Avanzate, Istituto Nazionale per la Ricerca sul Cancro, Largo Rosanna Benzi, 10, 16132 Genoa, Italy.
authors.forename: A
authors.initials: A
authors.lastname: Albini
authors.forename: S
authors.initials: S
authors.lastname: Ferrini
authors.forename: R
authors.initials: R
authors.lastname: Benelli
authors.forename: S
authors.initials: S
authors.lastname: Sforzini
authors.forename: D
authors.initials: D
authors.lastname: Giunciuglio
authors.forename: M G
authors.initials: MG
authors.lastname: Aluigi
authors.forename: A E
authors.initials: AE
authors.lastname: Proudfoot
authors.forename: S
authors.initials: S
authors.lastname: Alouani
authors.forename: T N
authors.initials: TN
authors.lastname: Wells
authors.forename: G
authors.initials: G
authors.lastname: Mariani
authors.forename: R L
authors.initials: RL
authors.lastname: Rabin
authors.forename: J M
authors.initials: JM
authors.lastname: Farber
authors.forename: D M
authors.initials: DM
authors.lastname: Noonan
mesh_terms: D000595:Amino Acid Sequence; D002118:Calcium / Q000378:metabolism*; D002478:Cells, Cultured; D018925:Chemokines / Q000737:chemistry / Q000494:pharmacology*; D002634:Chemotaxis, Leukocyte / Q000187:drug effects / Q000502:physiology*; D005434:Flow Cytometry; D015696:Gene Products, tat / Q000737:chemistry / Q000276:immunology* / Q000494:pharmacology*; D015497:HIV-1 / Q000276:immunology / Q000502:physiology; D006801:Humans; D008264:Macrophages / Q000187:drug effects / Q000502:physiology; D008969:Molecular Sequence Data; D009000:Monocytes / Q000187:drug effects / Q000502:physiology*; D010446:Peptide Fragments / Q000276:immunology / Q000494:pharmacology*; D016415:Sequence Alignment; D017386:Sequence Homology, Amino Acid; D015398:Signal Transduction / Q000187:drug effects / Q000502:physiology; D013601:T-Lymphocytes / Q000187:drug effects / Q000276:immunology / Q000502:physiology*; D054322:tat Gene Products, Human Immunodeficiency Virus
chemical_list: D018925:Chemokines; D015696:Gene Products, tat; D010446:Peptide Fragments; D054322:tat Gene Products, Human Immunodeficiency Virus; D002118:Calcium