EXCEPTIONAL FUSOGENICITY OF CHINESE-HAMSTER OVARY CELLS WITH MURINE RETROVIRUSES SUGGESTS ROLES FOR CELLULAR FACTOR(S) AND RECEPTOR CLUSTERS IN THE MEMBRANE-FUSION PROCESS

Chinese hamster ovary (CHO) cells are naturally resistant to infection by amphotropic and ecotropic murine retroviruses, but they become sus ceptible after expressing corresponding receptors rRAM-1 and mCAT-1, r espectively, and they then form abundant syncytia when exposed to thes e viruses, The fusogenic activities of CHO cell clones increase much m ore strongly with levels of receptor expression than do their suscepti bilities to infection, suggesting that the assembly of receptor cluste rs may limit syncytium formation, However, other cell lines are not fu sogenic, even if they express larger amounts of receptors. Our results suggest that a factor that is relatively abundant or active in CHO ce lls may functionally interact with rRAM-1 and mCAT-1 in a pathway that enables receptor-bearing membranes to fuse with membranes that contai n viral envelope glycoproteins, In the case of CHO/rRAM-1 cells, syncy tia form at foci of amphotropic 4070A virus infection by fusion-from-w ithin of infected with uninfected cells. This fusogenic propensity is a sole property of the uninfected CHO/rRAM-1 cells, which fuse in cocu ltures with any cells infected with 4070A virus, With CHO/mCAT-1 cells , fusogenicity is even greater and involves fusion-from-without by eco tropic virion particles, In contrast to infection, which behaves as ex pected for a process limited by ecotropic virus attachment to single r eceptors, fusion-from-without increases dramatically for cells that ex press the highest levels of mCAT-1. We propose that infection and sync ytium formation are limited at distinct steps of a common pathway that requires virus binding to a single receptor, assembly of multivalent virus-receptor complexes, structural changes in viral envelope glycopr oteins, and membrane fusion, The limiting step in syncytium formation is a cellular process that depends on receptor clustering and is relat ively active in CHO cells.