Transformation of rat fibroblasts and formation of virus-induced syncytia

Abstract

Human KC cells¹ and rat XC cells² transformed by Rous sarcoma virus (RSV) fuse to form multinucleate syncytia in the presence of several retroviruses^3–11, although neither cell line itself produces virus. XC cells form syncytia on co-cultivation with cells producing murine leukaemia virus (MuLV)³ and with purified MuLV⁴. This altered cytopathic property is readily quantified and is a useful assay both for titrating MuLV and for detecting cells producing these viruses^3,5,6. Fusion occurs from without and does not require viral replication⁷. We recently described the fu-1 cell line of developmentally defective rat myoblasts, which can also undergo synctia formation either by co-cultivation with cells infected with Moloney MuLV (MoMuLV) or on infection with intact or UV-inactivated MoMuLV¹². On chronic infection with MoMuLV, fu-1 cells become refractive to syncytia formation¹²; this is also true of XC and KC cells infected with their appropriate respective viruses^9,11,13. However, in contrast with XC and KC cells, fu-1 cells do release an endogenous retrovirus^14,15. Whereas XC, KC and fu-1 cells are transformed and can undergo virus-induced fusion, neither 118 MG cells¹⁰ nor L₈ myoblasts¹² (the non-transformed parents of KC and fu-1 cells, respectively), form these virus-induced syncytia. This suggests that the capacity of cells to undergo retrovirus-induced fusion rests with their transformed status. We report here that Rat-1 cells, transformed with the temperature-sensitive transformation mutant RSV-tsLA29 (ref. 16), only form syncytia in the presence of MoMuLV when these cells are preincubaated at 35 °C, the temperature permissive for transformation, and not at 40 °C, the non-permissive temperature. Rat-1 cells transformed with wild-type avian sarcoma virus form MoMuLV-induced syncytia at both temperatures. Thus, virus-induced transformation promotes changes in these cells that render them competent to undergo subsequent virus-induced fusion.