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 (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.
Albini
A
A
Centro di Biotecnologie Avanzate, Istituto Nazionale per la Ricerca sul Cancro, Largo Rosanna Benzi, 10, 16132 Genoa, Italy.
Ferrini
S
S
Benelli
R
R
Sforzini
S
S
Giunciuglio
D
D
Aluigi
M G
MG
Proudfoot
A E
AE
Alouani
S
S
Wells
T N
TN
Mariani
G
G
Rabin
R L
RL
Farber
J M
JM
Noonan
D M
DM
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
D018925:Chemokines; D015696:Gene Products, tat; D010446:Peptide Fragments; D054322:tat Gene Products, Human Immunodeficiency Virus; D002118:Calcium