Human erythrocytes bearing electroinserted CD4 neutralize infection in vitro by primary isolates of human immunodeficiency virus type 1.
Human erythrocytes bearing electroinserted full-length CD4 (RBC-CD4) can bind and fuse with a laboratory strain of human immunodeficiency virus type 1 (HIV-1) or with T cells infected by HIV-1. Here we show that RBC-CD4 neutralize primary HIV-1 strains in an assay of cocultivation of peripheral blood mononuclear cells (PBMC) from HIV-1-infected persons with uninfected PBMC. RBC-CD4 inhibited viral p24 core antigen accumulation in these cocultures up to 10,000-fold compared with RBC alone. Viral p24 accumulation was inhibited equally well when measured in culture supernatants or in call extracts. The inhibition was dose-dependent and long-lived. Two types of recombinant CD4 tested in parallel were largely ineffective. The neutralization of primary HIV-1 by RBC-CD4 in vitro was demonstrated in PBMC cultures from 21 of a total of 23 patients tested at two independent sites. RBC-CD4 may offer a route to blocking HIV-1 infection in vivo.
Tosi
P F
PF
Center for Blood Research Laboratory and Harvard Medical School, Boston, MA, USA.
Schwartz
D
D
Sharma
U
U
Mouneimne
Y
Y
Hannig
J
J
Li
G
G
McKinley
G
G
Grieco
M
M
Flexner
C W
CW
Lazarte
J
J
Norse
D
D
Nicolau
C
C
Volsky
D J
DJ
D000163:Acquired Immunodeficiency Syndrome / Q000097:blood; D001667:Binding, Competitive; D015704:CD4 Antigens / Q000235:genetics / Q000378:metabolism*; D015496:CD4-Positive T-Lymphocytes / Q000821:virology*; D002478:Cells, Cultured; D018920:Coculture Techniques; D018274:Electroporation; D004910:Erythrocyte Membrane / Q000378:metabolism; D004912:Erythrocytes / Q000821:virology*; D016655:HIV Core Protein p24 / Q000032:analysis; D015497:HIV-1 / Q000502:physiology*; D006801:Humans; D007700:Kinetics; D011994:Recombinant Proteins / Q000378:metabolism; D014779:Virus Replication
D015704:CD4 Antigens; D016655:HIV Core Protein p24; D011994:Recombinant Proteins