Recent studies indicate that viruses may influence
polyphosphoinositide levels. This study has examined the effects of vaccinia virus
infection on
phospholipase C activity.
Infection of BS-C-1 cells, an African Green Monkey kidney cell line, or A431 cells, a human
carcinoma cell line, with vaccinia virus inhibits receptor-mediated
phospholipase C activation. As a consequence, agonist-mediated Ca2+ mobilization in BS-C-1 cells also was inhibited by vaccinia virus
infection. Alleviation of the inhibition of
phospholipase C activation was observed in vaccinia virus-infected cells treated with
cycloheximide without influencing uninfected cells. Treatment of infected cells with
alpha-amanitin, an inhibitor of host
mRNA synthesis but not virus
mRNA synthesis, failed to alleviate the inhibition of
phospholipase C activation. Together these results suggest that a virus-encoded gene product mediates the inhibition of
phospholipase C activation without the need of a virus-induced host factor. Analysis of the processes involved in the formation of
inositol (1,4,5)-trisphosphate and mobilization of intracellular Ca2+ indicate that the vaccinia virus gene product exerts its inhibitory effects at the level of
phospholipase C activity. This may occur by either directly reducing the amount of
phospholipase C, reducing the specific activity of
phospholipase C, or by inhibiting the association of
phospholipase C with its substrate,
phosphatidylinositol 4,5-bisphosphate.