PKR-dependent autophagic degradation of herpes simplex virus type 1

Zsolt Tallóczy, Herbert W. Virgin IV, Beth Levine

Research output: Contribution to journalArticle

249 Scopus citations

Abstract

The lysosomal pathway of autophagy is the major catabolic mechanism for degrading long-lived cellular proteins and cytoplasmic organelles. Recent studies have also shown that autophagy (xenophagy) may be used to degrade bacterial pathogens that invade intracellularly. However, it is not yet known whether xenophagy is a mechanism for degrading viruses. Previously, we showed that autophagy induction requires the antiviral eIF2α kinase signaling pathway (including PKR and eIF2α) and that this function of eIF2α kinase signaling is antagonized by the herpes simplex virus (HSV-1) neurovirulence gene product, ICP34.5. Here, we show quantitative morphologic evidence of PKR-dependent xenophagic degradation of herpes simplex virions and biochemical evidence of PKR and eIF2α-dependent degradation of HSV-1 proteins, both of which are blocked by ICP34.5. Together, these findings indicate that xenophagy degrades HSV-1 and that this cellular function is antagonized by the HSV-1 neurovirulence gene product, ICP34.5. Thus, autophagy-related pathways are involved in degrading not only cellular constituents and intracellular bacteria, but also viruses.

Original languageEnglish (US)
Pages (from-to)24-29
Number of pages6
JournalAutophagy
Volume2
Issue number1
DOIs
StatePublished - Jan 1 2006

    Fingerprint

Keywords

  • Autophagy
  • Herpes simplex virus
  • PKR
  • Xenophagy
  • eIF2α kinase

ASJC Scopus subject areas

  • Molecular Biology
  • Cell Biology

Cite this