Neuronal injury due to HIV-1 envelope protein is blocked by anti-gp120 antibodies but not by anti-CD4 antibodies.
Picomolar concentrations of native or recombinant coat protein gp120, from the human immunodeficiency virus type 1 (HIV-1), injured rat retinal ganglion cell neurons in culture. This form of neurotoxicity could be completely abrogated by anti-gp120 but not by control preimmune serum, suggesting that the lethal effects of the purified preparations of the envelope protein were due to gp120 and not to a contaminant. Entry of HIV-1 is mediated by gp120 binding to a surface protein, designated "CD4," which is located, for example, on T lymphocytes. However, in the present study, specific anti-CD4 antibodies, at concentrations known to block effects mediated by high-affinity binding to CD4 on the surface of rat T cells, did not prevent neuronal injury induced by gp120. These findings suggest that injury of central neurons engendered by gp120 may be responsible, at least in part, for the neurologic manifestations observed in as many as 2/3 of the patients with acquired immunodeficiency syndrome, such as dementia, myelopathy, and visual loss, even in the absence of superinfection. In contrast with previous studies, however, this report suggests that the deleterious effects of gp120 on neurons may not be mediated via binding to the CD4 molecule.
Kaiser
P K
PK
Department of Neurology, Children's Hospital, Boston, MA 02115.
Offermann
J T
JT
Lipton
S A
SA
D000818:Animals; D000906:Antibodies / Q000276:immunology*; D015704:CD4 Antigens / Q000276:immunology* / Q000378:metabolism; D002478:Cells, Cultured; D015483:HIV Antibodies / Q000276:immunology*; D015699:HIV Envelope Protein gp120 / Q000009:adverse effects* / Q000276:immunology / Q000378:metabolism; D015497:HIV-1 / Q000378:metabolism*; D009474:Neurons / Q000378:metabolism / Q000473:pathology; D011485:Protein Binding; D051381:Rats; D011919:Rats, Inbred Strains; D011994:Recombinant Proteins / Q000009:adverse effects; D012165:Retinal Ganglion Cells / Q000378:metabolism / Q000473:pathology*
D000906:Antibodies; D015704:CD4 Antigens; D015483:HIV Antibodies; D015699:HIV Envelope Protein gp120; D011994:Recombinant Proteins