Ceramide regulates SR protein phosphorylation during adenoviral infection.
In this study, we show that adenoviral infection induced accumulation of the sphingolipid ceramide in a dose- and time-dependent manner. This accumulation preceded cell lysis, occurred in the absence of biochemical evidence of apoptosis, and was derived from de novo synthesis of ceramide. An adenovirus mutant that lacks the adenovirus death protein (ADP) produced ceramide accumulation in the absence of cell lysis. This suggested that ceramide accumulation was either driven by adenovirus or was a cellular stress response but was unlikely a result of cell death. The use of inhibitors of ceramide synthesis resulted in a significant delay in cell lysis, suggesting that ceramide was necessary for the lytic phase of the infection. Serine/arginine-rich (SR) proteins were dephosphorylated during the late phase of the viral cycle, and inhibitors of ceramide synthesis reversed this. These findings suggest that adenovirus utilizes the ceramide pathway to regulate SR proteins during infection.
Kanj
Souha S
SS
Department of Internal Medicine, American University of Beirut, Beirut, Lebanon.
Dandashi
Nadine
N
El-Hed
Aimee
A
Harik
Hisham
H
Maalouf
Maria
M
Kozhaya
Lina
L
Mousallem
Talal
T
Tollefson
Ann E
AE
Wold
William S
WS
Chalfant
Charles E
CE
Dbaibo
Ghassan S
GS
D000256:Adenoviridae / Q000502:physiology*; D015153:Blotting, Western; D016923:Cell Death; D002460:Cell Line; D002518:Ceramides / Q000037:antagonists & inhibitors / Q000096:biosynthesis / Q000378:metabolism*; D024161:Collagen Type XI / Q000378:metabolism; D004791:Enzyme Inhibitors / Q000494:pharmacology; D006801:Humans; D010750:Phosphoproteins / Q000378:metabolism*; D010766:Phosphorylation; D011506:Proteins / Q000737:chemistry / Q000378:metabolism*; D000068103:Serine-Arginine Splicing Factors
C499319:COL11A2 protein, human; D002518:Ceramides; D024161:Collagen Type XI; D004791:Enzyme Inhibitors; D010750:Phosphoproteins; D011506:Proteins; C000595776:SRSF8 protein, human; D000068103:Serine-Arginine Splicing Factors