Identification of a novel domain of HIV tat involved in monocyte chemotaxis.
Human immunodeficiency virus (HIV) Tat is chemotactic for monocytes and dendritic cells, an activity that could play a key role in the expansion of HIV infection of accessory cells. To date, domains of Tat previously found to interact with cell surface molecules have shown only partial chemotactic activity toward monocytes. Using overlapping Tat peptides, we identify a novel region of Tat with a potent chemotactic activity for monocytes, reaching levels equal to Tat itself. This peptide also provokes monocyte polarization similar to Tat and is able to compete with Tat for induction of monocyte migration. Specific high affinity (kd = 3 x 10(-9) M) cell surface binding sites on monocyte cell surfaces for this region of Tat are demonstrated. These data indicate that the majority of Tat effects on monocytes are mediated by a novel region in the cysteine-rich and core domains. These domains are highly conserved among different HIV isolates, suggesting an important role in the establishment of HIV infection.
Albini
A
A
Centro di Biotecnologie Avanzate, Istituto Nazionale per la Ricerca sul Cancro, Largo Rosanna Benzi, n10, 16132 Genova, Italy. albini@sirio.cba.unige.it
Benelli
R
R
Giunciuglio
D
D
Cai
T
T
Mariani
G
G
Ferrini
S
S
Noonan
D M
DM
D016764:Cell Polarity / Q000187:drug effects; D002634:Chemotaxis, Leukocyte / Q000187:drug effects; D015696:Gene Products, tat / Q000737:chemistry / Q000502:physiology*; D016325:HIV Long Terminal Repeat; D006801:Humans; D009000:Monocytes / Q000502:physiology*; D009240:N-Formylmethionine Leucyl-Phenylalanine / Q000494:pharmacology; D010446:Peptide Fragments / Q000494:pharmacology; D010449:Peptide Mapping
D015696:Gene Products, tat; D010446:Peptide Fragments; D009240:N-Formylmethionine Leucyl-Phenylalanine