[Successful prevention of rhinovirus infections with chimeric ICAM-1 immunoglobulin in vitro].
The intercellular adhesion molecule 1 (ICAM-1) is used as cellular receptor by 90% of human rhinoviruses (HRV). Recently, a recombinant, soluble ICAM-1 (sICAM-1) has been shown to be effective in prevention of the cytopathic effect of rhinovirus infection in vitro. Aim of this study was the production of molecules with multivalent binding sites. Different chimeric proteins were constructed by fusion of two or five extracellular domains of ICAM-1 with the constant regions of IgA1, IgM and IgG1 by polymerase chain reactions (PCR). IgA- and IgG-immunoadhesion molecules were expressed in eucaryotic cells as dimers, IgM-immunoadhesion molecules as decamers. Immunoadhesion molecules were compared to sICAM-1 for their ability to neutralize HRV: The chimeric protein of five N-terminal domains of ICAM-1 and the constant regions of IgA1 was 150 times more potent than sICAM-1 in neutralizing HRV. The first and the second N-terminal of ICAM-1 fused to IgA1 or IgM were five times more active, however, fused to IgG1 four times less active than sICAM-1. Sedimentation analyses of [H3]-leucin labled HRV after preincubation with the different immunoadhesion molecules showed a dose-dependent induction of a conformational change of the viral capsid proteins. The order of efficiency of the chimeric proteins was consistent to the neutralizing experiments. Our results showed that HRV neutralizing can be dramatically increased by multimerization of ICAM-1. The chimeric molecule between IgA1 and ICAM-1 seems to be a potential candidate for clinical testing to prevent and treat HRV-infections.
Martin
S
S
Klinische Abtelung, Diabetes-Forschungsinstitut, Düsseldorf.
Casanovas
J M
JM
Staunton
D E
DE
Springer
T A
TA
D015815:Cell Adhesion Molecules / Q000494:pharmacology*; D003588:Cytopathogenic Effect, Viral / Q000187:drug effects*; D004305:Dose-Response Relationship, Drug; D006801:Humans; D007136:Immunoglobulins / Q000494:pharmacology*; D018799:Intercellular Adhesion Molecule-1; D011991:Receptors, Virus / Q000187:drug effects; D011993:Recombinant Fusion Proteins / Q000494:pharmacology*; D012229:Rhinovirus / Q000187:drug effects*; D013329:Structure-Activity Relationship
D015815:Cell Adhesion Molecules; D007136:Immunoglobulins; D011991:Receptors, Virus; D011993:Recombinant Fusion Proteins; D018799:Intercellular Adhesion Molecule-1
Erfolgreiche Blockade von Rhinovirusinfektionen durch ICAM-1-Immunoglobulinchimäre in vitro.