Adhesion of human neuroblasts to HIV-1 tat.
Several neuropathologic findings in infants and children with human immunodeficiency virus type-1 (HIV-1) infection are different from those observed in adults, probably related to the fact that the retroviral infection occurs in the setting of neuro-development. This report describes the interaction and biologic activity of tat, the HIV-1 trans-activating protein on human neuroblasts. Two human neuroblastoma cell lines, LAN-5 and GI-CA-N, have been studied for their capability to adhere to tat (full recombinant protein) and to two different peptide residues of it. Both cells adhere to tat and tat46-60 basic domain, although not to tat65-80 residue, which contains the RGD (arginine-glycine-aspartic acid) motif. Adhesion to collagen I was inhibited by preincubating GI-CA-N cells with tat,46-60 although not with tat,65-80 indicating the capability of the basic residue to interfere with collagen I-induced cellular adhesion. The expression of 200-kD neurofilaments induced by collagen I was not induced by tat,46-60 indicating that neural differentiation along the same pathway is not mimicked by this peptide. Neuroblast cell proliferation was not affected by adhesion to tat46-60 nor to tat.65-80 GI-CA-N cells are not permissive to HIV-1 infection. However, proviral DNA was documented in the cell lysate for 14 consecutive in vitro passages, whereas HIV-1 transcription was never detectable. This would exclude the possibility that tat would be transduced by these cells. GI-CA-N stained negative for CD4, although positive for Gal-C, which may explain HIV-1 entry. Results show that immature human neural cells interact with tat protein and/or its basic residue in vitro. A mechanism similar to that herein described would possibly be active in vivo, which may help in clarifying the pathogenic mechanisms of neurologic dysfunction and destruction of the CNS observed in infants infected with HIV-1.
Cornaglia-Ferraris
P
P
Department of Pediatric Hematology/Oncology, G. Gaslini Children's Hospital, Genoa, Italy.
De Maria
A
A
Cirillo
C
C
Cara
A
A
Alessandri
G
G
D000595:Amino Acid Sequence; D002448:Cell Adhesion; D002455:Cell Division; D005109:Extracellular Matrix / Q000378:metabolism; D015696:Gene Products, tat / Q000378:metabolism*; D015497:HIV-1 / Q000378:metabolism*; D006801:Humans; D016023:Integrins / Q000378:metabolism; D008969:Molecular Sequence Data; D016900:Neurofilament Proteins / Q000378:metabolism; D009474:Neurons / Q000821:virology*; D011485:Protein Binding; D013329:Structure-Activity Relationship; D014407:Tumor Cells, Cultured; D054322:tat Gene Products, Human Immunodeficiency Virus
D015696:Gene Products, tat; D016023:Integrins; D016900:Neurofilament Proteins; D054322:tat Gene Products, Human Immunodeficiency Virus