Sequence and expression of a membrane-associated C-type lectin that exhibits CD4-independent binding of human immunodeficiency virus envelope glycoprotein gp120.
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.
Curtis
B M
BM
Bristol-Myers Squibb Pharmaceutical Research Institute, Seattle, WA 98121.
Scharnowske
S
S
Watson
A J
AJ
D000595:Amino Acid Sequence; D001483:Base Sequence; D002352:Carrier Proteins / Q000235:genetics / Q000378:metabolism*; D003001:Cloning, Molecular; D004247:DNA / Q000235:genetics; D015699:HIV Envelope Protein gp120 / Q000378:metabolism*; D006801:Humans; D037102:Lectins / Q000235:genetics / Q000378:metabolism*; D037241:Mannose-Binding Lectins; D008562:Membrane Glycoproteins / Q000235:genetics / Q000378:metabolism*; D008969:Molecular Sequence Data; D010920:Placenta; D011485:Protein Binding; D011991:Receptors, Virus / Q000235:genetics / Q000378:metabolism*
D002352:Carrier Proteins; D015699:HIV Envelope Protein gp120; D037102:Lectins; D037241:Mannose-Binding Lectins; D008562:Membrane Glycoproteins; D011991:Receptors, Virus; D004247:DNA