Analysis of the role of autophagy in replication of herpes simplex virus in cell culture

Diane E. Alexander, Stephen L. Ward, Noboru Mizushima, Beth Levine, David A. Leib

Research output: Contribution to journalArticle

108 Citations (Scopus)

Abstract

The herpes simplex virus type 1 (HSV-1) neurovirulence gene encoding 1CP34.5 controls the autophagy pathway. HSV-1 strains lacking ICP34.5 are attenuated in growth and pathogenesis in animal models and in primary cultured cells. While this growth defect has been attributed to the inability of an ICP34.5-null virus to counteract the induction of translational arrest through the PKR antiviral pathway, the role of autophagy in the regulation of HSV-1 replication is unknown. Here we show that HSV-1 infection induces autophagy in primary murine embryonic fibroblasts and that autophagosome formation is increased to a greater extent following infection with an ICP34.5-deficient virus. Elimination of the autophagic pathway did not significantly alter the replication of wild-type HSV-1 or ICP34.5 mutants. The phosphorylation state of eIF2α and viral protein accumulation were unchanged in HSV-1-infected cells unable to undergo autophagy. These data show that while ICP34.5 regulates autophagy, it is the prevention of translational arrest by ICP34.5 rather than its control of autophagy that is the pivotal determinant of efficient HSV-1 replication in primary cell culture.

Original languageEnglish (US)
Pages (from-to)12128-12134
Number of pages7
JournalJournal of Virology
Volume81
Issue number22
DOIs
StatePublished - Nov 2007

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Human herpesvirus 1
herpes simplex
autophagy
Autophagy
Human Herpesvirus 1
Simplexvirus
cell culture
Cell Culture Techniques
viruses
Virus Replication
Viruses
Primary Cell Culture
viral proteins
Viral Proteins
Virus Diseases
Growth
infection
cultured cells
Antiviral Agents
fibroblasts

ASJC Scopus subject areas

  • Immunology

Cite this

Analysis of the role of autophagy in replication of herpes simplex virus in cell culture. / Alexander, Diane E.; Ward, Stephen L.; Mizushima, Noboru; Levine, Beth; Leib, David A.

In: Journal of Virology, Vol. 81, No. 22, 11.2007, p. 12128-12134.

Research output: Contribution to journalArticle

Alexander, Diane E. ; Ward, Stephen L. ; Mizushima, Noboru ; Levine, Beth ; Leib, David A. / Analysis of the role of autophagy in replication of herpes simplex virus in cell culture. In: Journal of Virology. 2007 ; Vol. 81, No. 22. pp. 12128-12134.
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