Protection against fatal sindbis virus encephalitis by Beclin, a novel Bcl-2-interacting protein

Xiao Huan Liang, Linda K. Kleeman, Hui Hui Jiang, Gerald Gordon, James E. Goldman, Gail Berry, Brian Herman, Beth Levine

Research output: Contribution to journalArticle

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Abstract

bcl-2, the prototypic cellular antiapoptotic gene, decreases Sindbis virus replication and Sindbis virus-induced apoptosis in mouse brains, resulting in protection against lethal encephalitis. To investigate potential mechanisms by which Bcl-2 protects against Central nervous system Sindbis virus infection, we performed a yeast two-hybrid screen to identify Bcl-2- interacting gene products in an adult mouse brain library. We identified a novel 60-kDa coiled-coil protein, Beclin, which we confirmed interacts with Bcl-2 in mammalian cells, using fluorescence resonance energy transfer microscopy. To examine the role of Beclin in Sindbis virus pathogenesis, we constructed recombinant Sindbis virus chimeras that express full-length human Beclin (SIN/beclin), Beclin lacking the putative Bcl-2-binding domain (SIN/beclinΔBcl-2BD), or Beclin containing a premature stop codon near the 5' terminus (SIN/beclinstop). The survival of mice infected with SIN/beclin was significantly higher (71%) than the survival of mice infected with SIN/beclinΔBcl-2BD (9%) or SIN/beclinstop (7%) (P < 0.001). The brains of mice infected with SIN/beclin had fewer Sindbis virus RNA-positive cells, fewer apoptotic cells, and lower vital titers than the brains Of mice infected with SIN/beclinΔBcl-2BD or SIN/beclinstop. These findings demonstrate that Beclin is a novel Bcl-2-interacting cellular protein that may play a role in antiviral host defense.

Original languageEnglish (US)
Pages (from-to)8586-8596
Number of pages11
JournalJournal of Virology
Volume72
Issue number11
StatePublished - Nov 1998

Fingerprint

Sindbis virus
Sindbis Virus
Encephalitis
encephalitis
mice
brain
Proteins
proteins
Brain
bcl-2 Genes
Fluorescence Resonance Energy Transfer
stop codon
Nonsense Codon
chimerism
Virus Diseases
cells
Virus Replication
energy transfer
virus replication
lethal genes

ASJC Scopus subject areas

  • Immunology

Cite this

Liang, X. H., Kleeman, L. K., Jiang, H. H., Gordon, G., Goldman, J. E., Berry, G., ... Levine, B. (1998). Protection against fatal sindbis virus encephalitis by Beclin, a novel Bcl-2-interacting protein. Journal of Virology, 72(11), 8586-8596.

Protection against fatal sindbis virus encephalitis by Beclin, a novel Bcl-2-interacting protein. / Liang, Xiao Huan; Kleeman, Linda K.; Jiang, Hui Hui; Gordon, Gerald; Goldman, James E.; Berry, Gail; Herman, Brian; Levine, Beth.

In: Journal of Virology, Vol. 72, No. 11, 11.1998, p. 8586-8596.

Research output: Contribution to journalArticle

Liang, XH, Kleeman, LK, Jiang, HH, Gordon, G, Goldman, JE, Berry, G, Herman, B & Levine, B 1998, 'Protection against fatal sindbis virus encephalitis by Beclin, a novel Bcl-2-interacting protein', Journal of Virology, vol. 72, no. 11, pp. 8586-8596.
Liang XH, Kleeman LK, Jiang HH, Gordon G, Goldman JE, Berry G et al. Protection against fatal sindbis virus encephalitis by Beclin, a novel Bcl-2-interacting protein. Journal of Virology. 1998 Nov;72(11):8586-8596.
Liang, Xiao Huan ; Kleeman, Linda K. ; Jiang, Hui Hui ; Gordon, Gerald ; Goldman, James E. ; Berry, Gail ; Herman, Brian ; Levine, Beth. / Protection against fatal sindbis virus encephalitis by Beclin, a novel Bcl-2-interacting protein. In: Journal of Virology. 1998 ; Vol. 72, No. 11. pp. 8586-8596.
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