HSV-1 ICP34.5 confers neurovirulence by targeting the Beclin 1 autophagy protein.

HSV-1 ICP34.5 confers neurovirulence by targeting the Beclin 1 autophagy protein. Research Abstract Details 

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HSV-1 ICP34.5 confers neurovirulence by targeting the Beclin 1 autophagy protein. Abstract Text:

Anthony Orvedahl,Diane Alexander,Zsolt ,Qihua Sun,Yongjie Wei,Wei Zhang,Dennis Burns,David A Leib,Beth Levine,

Autophagy is postulated to play a role in antiviral innate immunity. However, it is unknown whether viral evasion of autophagy is important in disease pathogenesis. Here we show that the herpes simplex virus type 1 (HSV-1)-encoded neurovirulence protein ICP34.5 binds to the mammalian autophagy protein Beclin 1 and inhibits its autophagy function. A mutant HSV-1 virus lacking the Beclin 1-binding domain of ICP34.5 fails to inhibit autophagy in neurons and demonstrates impaired ability to cause lethal encephalitis in mice. The neurovirulence of this Beclin 1-binding mutant virus is restored in pkr(-/-) mice. Thus, ICP34.5-mediated antagonism of the autophagy function of Beclin 1 is essential for viral neurovirulence, and the antiviral signaling molecule PKR lies genetically upstream of Beclin 1 in host defense against HSV-1. Our findings suggest that autophagy inhibition is a novel molecular mechanism by which viruses evade innate immunity and cause fatal disease.

HSV-1 ICP34.5 confers neurovirulence by targeting the Beclin 1 autophagy protein. Publishing Authors By Initials

A Orvedahl,D Alexander,Z ,Q Sun,Y Wei,W Zhang,D Burns,DA Leib,B Levine,

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HSV-1 ICP34.5 confers neurovirulence by targeting the Beclin 1 autophagy protein. Journal Published:

PUBLICATION TYPE: Research Support, Non-U.S. Gov

Journal: Cell host & microbe

VOLUME: 1

Page Numbers: 23-35

Journal Abbreviation: Cell Host Microbe

ISSN: 1934-6069

DAY: 15

MONTH: Mar

YEAR: 2007

HSV-1 ICP34.5 confers neurovirulence by targeting the Beclin 1 autophagy protein. Information

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LANGUAGE: eng

NlmUniqueID: 101302316

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Grant and Affiliation Information for HSV-1 ICP34.5 confers neurovirulence by targeting the Beclin 1 autophagy protein.

AFFILIATION: Department of Internal Medicine, University of Texas Southwestern Medical Center, Dallas, TX 75390, USA.

Country: United States

AGENCY: United States NEI

GRANT: T32 EY13360-06

ACRONYM: EY

MEDLINETA: Cell Host Microbe

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