Exposure of Semliki Forest virus-infected baby hamster kidney cells to low pH leads to a proton influx and a rapid depletion of intracellular ATP which in turn prevents cell-cell fusion

Abstract

The conditions needed to trigger Semliki Forest virus (SFV) induced cell-cell fusion from within (FFWI) of baby hamster kidney (BHK) cells differs from some other cells (e.g., Aedes albopictus cells). In contrast to such cells it is mandatory for BHK cells to be brought back to a neutral pH after a short exposure to mildly acidic pH for fusion to occur. This phenomenon can be explained by a sudden drop of the intracellular pH observed after clamping the extracellular pH below 6.2--the pH required to trigger fusion--and by the thereby implied increased expenditure of ATP. Since the fusion from within of SFV-infected cells is energy dependent [Kempf et al. (1987) Arch Virol 95: 111-122] the fusion process is blocked due to the ATP depletion.

Low pH-induced Cell Fusion in Flavivirus-infected Aedes Albopictus Cell Cultures

“…Edwards & Brown (1984) made similar observations with Sindbis virus-infected mosquito cells; however, Kempf et al (1988) working with Semliki forest virus (SFV)-infected mosquito cells found that the cells fused whether they were left at low pH or returned to neutral pH. Similarly, we found that Sindbis virusinfected A. albopictus cells fused nearly as well when kept at pH 5.5 as when they were exposed briefly to pH 5-5 and then returned to pH 7.5.…”

“…To produce fusion of alphavirus-infected mammalian cells, cultures must be exposed to a low pH and then returned to neutral pH (Edwards & Brown, 1984;Kempf et al, 1988). Edwards & Brown (1984) made similar observations with Sindbis virus-infected mosquito cells; however, Kempf et al (1988) working with Semliki forest virus (SFV)-infected mosquito cells found that the cells fused whether they were left at low pH or returned to neutral pH.…”

“…Kempf et al (1987Kempf et al ( , 1988 reported, firstly, that fusion of SFV-infected vertebrate and mosquito cells is ATP-dependent and secondly, that in the case of vertebrate cells (BHK), but not mosquito cells, it was necessary, in order for fusion to occur, to return the ceils to neutral pH following exposure to acid pH. They hypothesized that when mosquito cells are exposed to an acidic medium they are still able to maintain a normal cytoplasmic pH and to provide sufficient ATP for fusion, but that vertebrate cells, in attempting to maintain a pH gradient in acidic medium, exhaust their ATP stores and therefore cannot fuse until the pH is returned to neutral.…”