Sequence and expression of a membrane-associated C-type lectin that exhibits CD4-independent binding of human immunodeficiency virus envelope glycoprotein gp120

Proc Natl Acad Sci U S A. 1992 Sep 1;89(17):8356-60. doi: 10.1073/pnas.89.17.8356.

Abstract

The binding of the human immunodeficiency virus (HIV) envelope glycoprotein gp120 to the cell surface receptor CD4 has been considered a primary determinant of viral tropism. A number of cell types, however, can be infected by the virus, or bind gp120, in the absence of CD4 expression. Human placenta was identified as a tissue that binds gp120 in a CD4-independent manner. A placental cDNA library was screened by expression cloning and a cDNA (clone 11) encoding a gp120-binding protein unrelated to CD4 was isolated. The 1.3-kilobase cDNA predicts a protein of 404 amino acids with a calculated M(r) of 45,775 and organized into three domains: an N-terminal cytoplasmic and hydrophobic region, a set of seven complete and one incomplete tandem repeat, and a C-terminal domain with homology to C-type (calcium-dependent) lectins. A type II membrane orientation (N-terminal cytoplasmic) is predicted both by the cDNA sequence and by the reactivity of C-terminal peptide-specific antiserum with the surface of clone 11 transfected cells. Native and recombinant gp120 and whole virus bind transfected cells. gp120 binding is high affinity (kd, 1.3-1.6 nM) and inhibited by mannan, D-mannose, and L-fucose; once bound, gp120 is internalized rapidly. Collectively, these data demonstrate that the gp120-binding protein is a membrane-associated mannose-binding lectin. Proteins of this type may play an important role in the CD4-independent association of HIV with cells.

MeSH terms

  • Amino Acid Sequence
  • Base Sequence
  • Carrier Proteins / genetics
  • Carrier Proteins / metabolism*
  • Cloning, Molecular
  • DNA / genetics
  • HIV Envelope Protein gp120 / metabolism*
  • Humans
  • Lectins / genetics
  • Lectins / metabolism*
  • Mannose-Binding Lectins
  • Membrane Glycoproteins / genetics
  • Membrane Glycoproteins / metabolism*
  • Molecular Sequence Data
  • Placenta
  • Protein Binding
  • Receptors, Virus / genetics
  • Receptors, Virus / metabolism*

Substances

  • Carrier Proteins
  • HIV Envelope Protein gp120
  • Lectins
  • Mannose-Binding Lectins
  • Membrane Glycoproteins
  • Receptors, Virus
  • DNA

Associated data

  • GENBANK/M98457