Inhibition of HIV type 1 infection with a RANTES-IgG3 fusion protein.
The natural ligands for the chemokine receptors CCR5 (RANTES, MIP-1alpha, and MIP-1beta) and CXCR4 (SDF-1) can act as potent inhibitors of infection by the human immunodeficiency virus type 1 (HIV-1) at the level of viral entry. Unlike antibody-mediated inhibition, chemokine-mediated inhibition is broadly effective. Different HIV-1 strains can utilize the same coreceptor(s) for viral entry and, therefore, can be blocked by the same chemokine(s). HIV-1 strains that are highly resistant to neutralization by V3-specific antibodies are sensitive to inhibition by chemokines. Therefore, the use of chemokine-derived molecules constitutes a potential therapeutic approach to prevent infection by HIV-1. We have generated a fusion protein between RANTES and human IgG3 (RANTES-IgG3). The effectiveness of RANTES-IgG3 inhibition of infection by HIV-1 was similar to that of rRANTES. Inhibition of HIV-1 by RANTES-IgG3 was specific for CCR5-dependent but not CXCR4-dependent HIV-1 isolates. Fusion of a chemokine to an IgG moiety offers two desirable properties with respect to the recombinant chemokine alone. First, IgG fusion proteins have extended half-lives in vivo. Second, molecules with IgG heavy chain moieties may be able to cross the placenta and potentially induce fetal protection.
Challita-Eid
P M
PM
Department of Medicine, University of Rochester Cancer Center, New York 14642, USA.
Klimatcheva
E
E
Day
B T
BT
Evans
T
T
Dreyer
K
K
Rimel
B J
BJ
Rosenblatt
J D
JD
Planelles
V
V
D002478:Cells, Cultured; D018946:Chemokine CCL5 / Q000276:immunology*; D004797:Enzyme-Linked Immunosorbent Assay; D015497:HIV-1 / Q000276:immunology* / Q000502:physiology; D006801:Humans; D007074:Immunoglobulin G / Q000276:immunology*; D008561:Membrane Fusion / Q000276:immunology; D009500:Neutralization Tests; D019718:Receptors, CXCR4 / Q000378:metabolism; D011993:Recombinant Fusion Proteins / Q000276:immunology* / Q000378:metabolism
D018946:Chemokine CCL5; D007074:Immunoglobulin G; D019718:Receptors, CXCR4; D011993:Recombinant Fusion Proteins