Characterization of in vitro inhibition of human immunodeficiency virus by purified recombinant CD4.
The first step in infection of human T cells with human immunodeficiency virus (HIV) is binding of viral envelope glycoprotein gp120 to its cellular receptor, CD4. The specificity of this interaction has led to the development of soluble recombinant CD4 (rCD4) as a potential antiviral and therapeutic agent. We have previously shown that crude preparations of rCD4 can indeed block infection of T cells by HIV type 1 (HIV-1). Here we present a more detailed analysis of this antiviral activity, using HIV-1 infection of the T lymphoblastoid cell line H9 as a model. Purified preparations of rCD4 blocked infection in this system at nanomolar concentrations; combined with the known affinity of the CD4-gp120 interaction, this finding suggests that the inhibition is simply due to competition for gp120 binding. As predicted, rCD4 had comparable activity against all strains of HIV-1 tested and significant activity against HIV-2. Higher concentrations of rCD4 blocked infection even after the virus had been adsorbed to the cells. These findings imply that the processes of viral adsorption and penetration require different numbers of gp120-CD4 interactions. Recombinant CD4 was able to prevent the spread of HIV infection in mixtures of uninfected and previously infected cells. Our studies support the notion that rCD4 is a potent antiviral agent, effective against a broad range of HIV-1 isolates, and demonstrate the value of purified rCD4 as an experimental tool for studying the mechanism of virus entry into cells.
Byrn
R A
RA
Department of Medicine, Harvard Medical School, New England Deaconess Hospital, Boston, Massachusetts 02215.
Sekigawa
I
I
Chamow
S M
SM
Johnson
J S
JS
Gregory
T J
TJ
Capon
D J
DJ
Groopman
J E
JE
D000327:Adsorption; D000945:Antigens, Differentiation, T-Lymphocyte; D000954:Antigens, Surface / Q000502:physiology*; D002460:Cell Line; D006678:HIV / Q000254:growth & development*; D015699:HIV Envelope Protein gp120; D015728:Receptors, HIV; D011991:Receptors, Virus / Q000502:physiology*; D011994:Recombinant Proteins; D012191:Retroviridae Proteins / Q000032:analysis
D000945:Antigens, Differentiation, T-Lymphocyte; D000954:Antigens, Surface; D015699:HIV Envelope Protein gp120; D015728:Receptors, HIV; D011991:Receptors, Virus; D011994:Recombinant Proteins; D012191:Retroviridae Proteins