PREVENTION OF RHINOVIRUS INFECTION INVITRO BY ICAM-1 IMMUNOGLOBULIN CHIMERAS

The intercellular adhesion molecule 1 (ICAM-1) is used as cellular rec eptor by 90% of human rhinoviruses (HRV). Recently, a recombinant, sol uble ICAM-1 (sICAM-1) has been shown to be effective in prevention of the cytopathic effect of rhinovirus infection in vitro [7]. Aim of thi s study [8] was the production of molecules with multivalent binding s ites. Different chimeric proteins were constructed by fusion of two or five extracellular domains of ICAM-1 with the constant regions of IgA 1, IgM and IgG1 by polymerase chain reactions (PCR). IgA- and IgG-immu noadhesion molecules were expressed in eucaryotic cells as dimers, IgM -immunoadhesion molecules as decamers. Immunoadhesion molecules were c ompared to sICAM-1 for their ability to neutralize HRV: The chimeric p rotein of five N-terminal domains of ICAM-1 and the constant regions o f 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 f ive times more active, however, fused to IgG1 four times less active t han sICAM-1. Sedimentation analyses of [H-3]-leucin labled HRV after p reincubation with the different immunoadhesion molecules showed a dose -dependent induction of a conformational change of die viral capsid pr oteins. The order of efficiency of the chimeric proteins was consisten t to the neutralizing experiments. Our results showed that HRV neutral izing can be dramatically increased by multimerization of ICAM-1. The chimeric molecule between IgA1 and ICAM-1 seems to be a potential cand idate for clinical testing to prevent and treat HRV-infections.