Enhancement of thermal effect in virally infected mammalian cells in vitro and its modification by chlorpromazine.

ABSTRACT

NIH/3T3 cells chronically infected with Moloney murine leukemia virus (M-MuLV) were more thermosensitive than uninfected cells. Cells upregulated by a primary dose of heat formed giant colonies and had an altered response to a second dose of heat. Thermosensitivity depended upon the time elapsed between heat treatments. Heating the cells at either 42 degrees or 42.5 degrees C yielded biphasic survival curves, indicating a mixed population of productively infected and quiescent cells. Hyperthermia at 43 degrees C abolished this effect. Thermal sensitivity of infected cells was correlated with the expression of a viral reporter protein. Chlorpromazine (CPZ), a membrane active drug potentiated the heat effect in both uninfected and virally infected cells. The drug also abolished the biphasic effect of heat in infected cells, suggesting that heat sensitivity of both productively and quiescent cells is membrane mediated. The combined effect of heat at 42.5 degrees C and CPZ was equivalent to the effect of heat alone at 43.5 degrees C. These observations indicate that heat can selectively be lethal to productively infected cells and the membrane active drugs could further amplify this hyperthermic effect.