Transgenesis offers many ways to obtain virus-resistant plants. However, in most cases resistance is against a single virus or viral strain. We have taken a novel approach based on the ability of a whitefly endosymbiotic GroEL to bind viruses belonging to several genera, in vivo and in vitro. We have expressed the GroEL gene in Nicotiana benthamiana plants, postulating that upon virus inoculation, GroEL will bind to virions, thereby interfering with pathogenesis. The transgenic plants were inoculated with the begomovirus tomato yellow leaf curl virus (TYLCV) and the cucumovirus cucumber mosaic virus (CMV), both of which interacted with GroEL in vitro, and with the trichovirus grapevine virus A (GVA) and the tobamovirus tobacco mosaic virus (TMV), which did not. While the transgenic plants inoculated with TYLCV and CMV presented a high level of tolerance, those inoculated with GVA and TMV were susceptible. The amounts of virus in tolerant transgenic plants was lower by three orders of magnitude than those in non-transgenic plants; in comparison, the amounts of virus in susceptible transgenic plants were similar to those in non-transgenic plants. Leaf extracts of the tolerant plants contained GroEL-virus complexes. Hence, tolerance was correlated with trapping of viruses in planta. This study demonstrated that multiple resistances to viruses belonging to several different taxonomic genera could be achieved. Moreover, it might be hypothesized that plants expressing GroEL will be tolerant to those viruses that bind to GroEL in vitro, such as members of the genera Begomovirus, Cucumovirus, Ilarvirus, Luteovirus, and Tospovirus.