Human cytomegalovirus carries a cell-derived phospholipase A2 required for infectivity.
Human cytomegalovirus (HCMV) is known to carry host cell-derived proteins and mRNAs whose role in cell infection is not understood. We have identified a phospholipase A2 (PLA2) activity borne by HCMV by using an assay based on the hydrolysis of fluorescent phosphatidylcholine. This activity was found in all virus strains analyzed and in purified strains. It was calcium dependent and was sensitive to inhibitors of cytosolic PLA2 (cPLA2) but not to inhibitors of soluble PLA2 or calcium-independent PLA2. No other phospholipase activity was detected in the virus. Purified virus was found to contain human cellular cPLA2alpha, as detected by monoclonal antibody. No homology with PLA2 was found in the genome of HCMV, indicating that HCMV does not code for a PLA2. Decreased de novo expression of immediate-early proteins 1 and 2 (IE1 and IE2), tegument phosphoprotein pp65, and virus production was observed when HCMV was treated with inhibitors of cPLA2. Cell entry of HCMV was not altered by those inhibitors, suggesting the action of cPLA2 was postentry. Together, our results indicate a selective sorting of a cell-derived cPLA2 during HCMV maturation, which is further required for infectivity.
Allal
Cuider
C
INSERM U563, Toulouse, CPTP, Institut Claude de Préval, IFR30, CHU Purpan, 31059 Toulouse Cedex, France.
Buisson-Brenac
Claire
C
Marion
Vincent
V
Claudel-Renard
Clotilde
C
Faraut
Thomas
T
Dal Monte
Paola
P
Streblow
Daniel
D
Record
Michel
M
Davignon
Jean-Luc
JL
D002478:Cells, Cultured; D003587:Cytomegalovirus / Q000201:enzymology* / Q000472:pathogenicity*; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005347:Fibroblasts / Q000201:enzymology* / Q000821:virology; D006801:Humans; D018613:Microscopy, Confocal; D008856:Microscopy, Fluorescence; D010713:Phosphatidylcholines / Q000378:metabolism; D010741:Phospholipases A / Q000037:antagonists & inhibitors / Q000378:metabolism*; D054467:Phospholipases A2
D004791:Enzyme Inhibitors; D010713:Phosphatidylcholines; D010741:Phospholipases A; D054467:Phospholipases A2