Altered cholesterol trafficking in herpesvirus-infected arterial cells. Evidence for viral protein kinase-mediated cholesterol accumulation. Academic Article uri icon

Overview

MeSH

  • Biological Transport
  • Cells, Cultured
  • Cholesterol Esters
  • Humans
  • Hydroxymethylglutaryl CoA Reductases
  • RNA, Messenger
  • Receptors, LDL

MeSH Major

  • Arteries
  • Cholesterol, LDL
  • Herpesvirus 1, Human
  • Protein Kinases

abstract

  • Herpesvirus infection of arterial smooth muscle cells has been shown to cause cholesteryl ester (CE) accumulation. However, the effects of human herpes simplex virus type 1 (HSV-1) infection on cholesterol binding and internalization, intracellular metabolism, and efflux have not been evaluated. In addition, the effects of viral infection on signal transduction pathways that impact upon cholesterol metabolism have not been studied. We show in studies reported herein that HSV-1 infection of arterial smooth muscle cells enhances low density lipoprotein (LDL) binding and uptake which parallels an increase in LDL receptor steady state mRNA levels and transcription of the LDL receptor gene. HSV-2 also increases CE synthesis and 3-hydroxy- 3-methylglutaryl-CoA reductase activity but concomitantly reduces CE hydrolysis and cholesterol efflux. Interestingly, this viral infection was associated with a time-dependent decrease in protein kinase A activity and an increase in viral-induced protein kinase (VPK) activity commensurate with the accumulation of esterified cholesterol. The relationship between increased VPK activity and alterations in CE accumulation in virally infected cells was explored using an HSV-1 VPK- mutant in which the portion of the HSV-1 genome encoding VPK had been deleted. Cholesteryl ester accumulation was significantly increased (> 50-fold) in HSV-1-infected cells compared to uninfected cells. However, the HSV-1 VPK- mutant had no significant effect on CE accumulation. The relationship between VPK activity and these alterations in cholesterol metabolism was further supported by the observation that staurosporine and calphostin C (protein kinase inhibitors) reduced protein kinase activity in HSV-1-infected cells. These results suggest several potential mechanisms by which alterations in kinase activities in response to HSV-1 infection of vascular cells may alter cholesterol trafficking processes that eventually lead to CE accumulation.

publication date

  • August 18, 1995

has subject area

  • Arteries
  • Biological Transport
  • Cells, Cultured
  • Cholesterol Esters
  • Cholesterol, LDL
  • Herpesvirus 1, Human
  • Humans
  • Hydroxymethylglutaryl CoA Reductases
  • Protein Kinases
  • RNA, Messenger
  • Receptors, LDL

Research

keywords

  • Journal Article

Identity

Language

  • eng

PubMed ID

  • 7642651

Additional Document Info

start page

  • 19630

end page

  • 19637

volume

  • 270

number

  • 33