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PMID: 17855538 Published · ppublish English Journal Article Research Support, N.I.H., Extramural Research Support, Non-U.S. Gov't

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

Journal of virology ·Vol. 81 ·No. 22 ·2007-11-00 ·Pages 12128-34

Alexander DE, Ward SL, Mizushima N, Levine B, Leib DA

Abstract

The herpes simplex virus type 1 (HSV-1) neurovirulence gene encoding ICP34.5 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 eIF2alpha 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.

MeSH Terms
Animals Autophagy/genetics Autophagy-Related Protein 5 Cells, Cultured Eukaryotic Initiation Factor-2/metabolism Fibroblasts/virology Mice Mice, Mutant Strains Microtubule-Associated Proteins/genetics Phosphorylation Simplexvirus/genetics,physiology Viral Proteins/genetics Virus Replication/genetics
Chemicals
Atg5 protein, mouse Autophagy-Related Protein 5 Eukaryotic Initiation Factor-2 Microtubule-Associated Proteins Viral Proteins gamma 34.5 protein, Human herpesvirus 1
Authors & Affiliations
5 authors, click to expand affiliations / ORCID
Alexander Diane E
Department of Ophthalmology, Washington University School of Medicine, St Louis, MO 63110, USA.
Ward Stephen L
Mizushima Noboru
Levine Beth
Leib David A
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Article Info
Journal
Journal of virology
Abbr.
J Virol
ISSN
0022-538X
DOI
10.1128/JVI.01356-07
Published
2007-11-00
Epub
2007-00-12
Pages
12128-34
Language
English
Region
United States
NLM ID
0113724
PMCID
PMC2169004
Subset
IM
Grants
NEI NIH HHS · P30 EY002687 · United States
NEI NIH HHS · T32 EY013360 · United States
NEI NIH HHS · R01 EY09083 · United States
NEI NIH HHS · P30 EY02687 · United States
NEI NIH HHS · R01 EY009083 · United States
NIAID NIH HHS · R01 AI051367 · United States
NEI NIH HHS · 5 T32 EY13360-06 · United States
External Links
PubMed source DOI: 10.1128/JVI.01356-07 PMC Full Text View journal details
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