Decreased messenger RNA translation in herpesvirus-infected arterial cells: effects on cholesteryl ester hydrolase.
Herpes simplex viruses (HSVs) contain a function that can cause the degradation of host mRNA and mediate the shutoff of host protein synthesis. Previously, we observed that HSV infection causes a 40-fold increase in cholesteryl ester (CE) accretion in arterial smooth muscle cells due, in part, to a substantial decrease in CE hydrolysis. In studies reported herein, we found that HSV infection leads to reduced immunoprecipitable lysosomal (acid) CE hydrolase (ACEH) and beta-galactosidase, another lysosomal enzyme in vascular smooth muscle cells. The HSV-induced reduction was greater with respect to ACEH than beta-galactosidase. To determine whether degradation of host cellular mRNA or inhibition of cellular translation was responsible for decreased CE hydrolysis in HSV-infected smooth muscle cells, we utilized an in vitro translation system that permitted us to compensate for any mRNA degradation during viral infection. Reduced ACEH activity was observed in the total cellular RNA translation products of HSV-infected smooth muscle cells compared to uninfected cells owing to posttranscriptional modification. We conclude that the decrease in CE hydrolysis in HSV-infected smooth muscle cells is caused primarily by decreased ACEH synthesis and activity, which can contribute to CE accretion in these vascular cells.
Hajjar
D P
DP
Department of Biochemistry, National Institutes of Health Specialized Centers of Research in Thrombosis, New York, NY 10021.
Nicholson
A C
AC
Hajjar
K A
KA
Sando
G N
GN
Summers
B D
BD
D000818:Animals; D001013:Aorta, Thoracic; D002265:Carboxylic Ester Hydrolases / Q000378:metabolism*; D002417:Cattle; D002788:Cholesterol Esters / Q000378:metabolism; D007163:Immunosorbent Techniques; D008247:Lysosomes / Q000201:enzymology; D009131:Muscle, Smooth, Vascular / Q000378:metabolism* / Q000382:microbiology; D014176:Protein Biosynthesis; D012333:RNA, Messenger / Q000378:metabolism*; D018139:Simplexvirus / Q000502:physiology*; D002787:Sterol Esterase / Q000378:metabolism*; D001616:beta-Galactosidase / Q000378:metabolism
D002788:Cholesterol Esters; D012333:RNA, Messenger; D002265:Carboxylic Ester Hydrolases; D002787:Sterol Esterase; D001616:beta-Galactosidase