A soluble CD4 protein selectively inhibits HIV replication and syncytium formation.
The CD4 (T4) molecule is expressed on a subset of T lymphocytes involved in class II MHC recognition, and is probably the physiological receptor for one or more monomorphic regions of class II MHC (refs 1-3). CD4 also functions as a receptor for the human immunodeficiency virus (HIV) exterior envelope glycoprotein (gp120) (refs 4-9), being essential for virus entry into the host cell and for membrane fusion, which contributes to cell-to-cell transmission of the virus and to its cytopathic effects. We have used a baculovirus expression system to generate mg quantities of a hydrophilic extracellular segment of CD4. Concentrations of soluble CD4 in the nanomolar range, like certain anti-CD4 monoclonal antibodies, inhibit syncytium formation and HIV infection by binding gp120-expressing cells. Perhaps more importantly, class II specific T-cell interactions are uninhibited by soluble CD4 protein, whereas they are virtually abrogated by equivalent amounts of anti-T4 antibody. This may reflect substantial differences in CD4 affinity for gp120 and class II MHC.
Hussey
R E
RE
Laboratories of Immunobiology, Dana-Farber Cancer Institute, Boston, Massachusetts 02115.
Richardson
N E
NE
Kowalski
M
M
Brown
N R
NR
Chang
H C
HC
Siliciano
R F
RF
Dorfman
T
T
Walker
B
B
Sodroski
J
J
Reinherz
E L
EL
D000818:Animals; D000945:Antigens, Differentiation, T-Lymphocyte / Q000378:metabolism*; D001667:Binding, Competitive; D002459:Cell Fusion; D002460:Cell Line; D006224:Cricetinae; D003412:Cricetulus; D005260:Female; D005347:Fibroblasts / Q000378:metabolism; D006678:HIV / Q000502:physiology*; D015699:HIV Envelope Protein gp120; D006801:Humans; D010053:Ovary; D015728:Receptors, HIV; D011991:Receptors, Virus / Q000378:metabolism*; D011993:Recombinant Fusion Proteins / Q000378:metabolism / Q000494:pharmacology*; D011994:Recombinant Proteins / Q000494:pharmacology*; D012191:Retroviridae Proteins / Q000378:metabolism; D012995:Solubility; D013601:T-Lymphocytes / Q000378:metabolism; D014779:Virus Replication
D000945:Antigens, Differentiation, T-Lymphocyte; D015699:HIV Envelope Protein gp120; D015728:Receptors, HIV; D011991:Receptors, Virus; D011993:Recombinant Fusion Proteins; D011994:Recombinant Proteins; D012191:Retroviridae Proteins