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

828 Scopus citations

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 1 1998

ASJC Scopus subject areas

  • Microbiology
  • Immunology
  • Insect Science
  • Virology

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