Tethered antibodies and virus resistance

Antibodies can be anchored to the plasma membrane of cells for specific functions. Jia Xie et al. (pp. 4655–4660) used such an approach to bind membrane-tethered antibodies (MTA) to cell surface receptors that doubled as virus receptors to render cells resistant to viral infection. The authors delivered MTAs that targeted the rhinovirus A and B receptor into HeLa cells before exposing the cells to rhinovirus. Of the surviving cells, cells expressing protective MTAs were more likely to survive rhinovirus exposure than cells with MTAs that had been selected only for binding. By adjusting the antibody’s antigen-binding site, the authors improved the likelihood of T-cell attachment, while maintaining virus-neutralizing capabilities. Further, the authors engineered HeLa-derived cells to express MTAconfigured CD4 antibodies. The cells demonstrated almost complete inhibition of infection for four of six HIV isolates tested as well as significant protection for the remaining isolates. In both experiments, cells were more likely to survive if they contained MTAs than if they contained the same antibodies in soluble form. According to the authors, attaching MTAs to virus receptors may help generate virusresistant cells, and resistant cells may have a selective advantage. - Read at PNAS