Inhibition of agonist-induced activation of phospholipase C following poxvirus infection.
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.
Oliver
K G
KG
Laboratory of Cellular and Molecular Pharmacology, National Institute of Environmental Health Sciences, National Institutes of Health, Research Triangle Park, North Carolina 27709.
Buller
R M
RM
Hughes
P J
PJ
Putney
J W
JW
Palumbo
G J
GJ
D000255:Adenosine Triphosphate / Q000378:metabolism / Q000494:pharmacology; D000546:Amanitins / Q000494:pharmacology; D000818:Animals; D002118:Calcium / Q000378:metabolism; D002294:Carcinoma, Squamous Cell; D002460:Cell Line; D002472:Cell Transformation, Viral; D002522:Chlorocebus aethiops; D003513:Cycloheximide / Q000494:pharmacology; D004789:Enzyme Activation; D006801:Humans; D007294:Inositol / Q000378:metabolism; D015544:Inositol 1,4,5-Trisphosphate / Q000378:metabolism; D007295:Inositol Phosphates / Q000302:isolation & purification / Q000378:metabolism*; D007668:Kidney; D007700:Kinetics; D012333:RNA, Messenger / Q000096:biosynthesis / Q000187:drug effects; D014407:Tumor Cells, Cultured; D010738:Type C Phospholipases / Q000037:antagonists & inhibitors / Q000378:metabolism*; D014616:Vaccinia virus / Q000235:genetics*
D000546:Amanitins; D007295:Inositol Phosphates; D012333:RNA, Messenger; D007294:Inositol; D015544:Inositol 1,4,5-Trisphosphate; D000255:Adenosine Triphosphate; D003513:Cycloheximide; D010738:Type C Phospholipases; D002118:Calcium