Effects of anti-gp120 monoclonal antibodies on CD4 receptor binding by the env protein of human immunodeficiency virus type 1 - PubMed (original) (raw)

Comparative Study

Effects of anti-gp120 monoclonal antibodies on CD4 receptor binding by the env protein of human immunodeficiency virus type 1

P S Linsley et al. J Virol. 1988 Oct.

Abstract

Monoclonal antibodies (MAbs) to defined peptide epitopes on gp120 from human immunodeficiency virus type 1 were used to investigate the involvement of their epitopes in gp120 binding to the CD4 receptor. Recombinant vaccinia viruses were constructed that expressed either full-length gp120 (v-ED6), or a truncated gp120 lacking 44 amino acids at the carboxyl terminus (v-ED4). Binding of these glycoproteins to the CD4 receptor was detected directly with metabolically labeled gp120 or indirectly with the gp120 MAbs. Truncated gp120 from v-ED4 bound to CD4-positive cells less than 1/12 as well as gp120 from v-ED6, indicating that the C-terminal region of gp120, which is conserved in numerous isolates of human immunodeficiency virus type 1, is critical for CD4 binding. However, MAb 110-1, which recognizes a peptide contained in the region deleted from v-ED4 (amino acids 489 through 511), did not inhibit binding of gp120 to CD4. MAb 110-1 also reacted with gp120 bound to the CD4 receptor, indicating that the epitope for this antibody does not directly interact with CD4. A second MAb, 110-4, which recognizes a peptide epitope located between amino acids 303 and 323 and has potent viral neutralizing activity, also bound to gp120 on the CD4 receptor. Furthermore, pretreatment of gp120 with MAb 110-4 at concentrations approximately 1,000-fold higher than those required for complete virus neutralization inhibited subsequent CD4 binding by only about 65%. Taken together, these data suggest that neutralization mediated by antibody 110-4 does not result from binding of this MAb to the CD4-binding site of gp120.

PubMed Disclaimer

Cited by

Neutralizing antibodies against the V3 loop of human immunodeficiency virus type 1 gp120 block the CD4-dependent and -independent binding of virus to cells.
Valenzuela A, Blanco J, Krust B, Franco R, Hovanessian AG. Valenzuela A, et al. J Virol. 1997 Nov;71(11):8289-98. doi: 10.1128/JVI.71.11.8289-8298.1997. J Virol. 1997. PMID: 9343181 Free PMC article.
Inhibition of virus attachment to CD4+ target cells is a major mechanism of T cell line-adapted HIV-1 neutralization.
Ugolini S, Mondor I, Parren PW, Burton DR, Tilley SA, Klasse PJ, Sattentau QJ. Ugolini S, et al. J Exp Med. 1997 Oct 20;186(8):1287-98. doi: 10.1084/jem.186.8.1287. J Exp Med. 1997. PMID: 9334368 Free PMC article.
Possible role of the V3 domain of gp120 in resistance to an amphotericin B derivative (MS8209) blocking human immunodeficiency virus entry.
Pleskoff O, Sol N, Marrakchi H, Serlin M, Seman M, Alizon M. Pleskoff O, et al. J Virol. 1996 Nov;70(11):8247-51. doi: 10.1128/JVI.70.11.8247-8251.1996. J Virol. 1996. PMID: 8892962 Free PMC article.
Reduced cell surface expression of processed human immunodeficiency virus type 1 envelope glycoprotein in the presence of Nef.
Schwartz O, Rivière Y, Heard JM, Danos O. Schwartz O, et al. J Virol. 1993 Jun;67(6):3274-80. doi: 10.1128/JVI.67.6.3274-3280.1993. J Virol. 1993. PMID: 8497051 Free PMC article.

References

1. Rev Infect Dis. 1980 Jan-Feb;2(1):40-61 - PubMed
1. J Virol. 1988 Jan;62(1):139-47 - PubMed
1. J Virol. 1984 Mar;49(3):857-64 - PubMed
1. Science. 1984 May 4;224(4648):497-500 - PubMed
1. J Gen Virol. 1984 Jun;65 ( Pt 6):1015-22 - PubMed

Effects of anti-gp120 monoclonal antibodies on CD4 receptor binding by the env protein of human immunodeficiency virus type 1 - PubMed (original) (raw)