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Protection against fatal Sindbis virus encephalitis by beclin, a novel Bcl-2-interacting protein.

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/beclinDeltaBcl-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/beclinDeltaBcl-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 viral titers than the brains of mice infected with SIN/beclinDeltaBcl-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.

Pubmed ID: 9765397


  • Liang XH
  • Kleeman LK
  • Jiang HH
  • Gordon G
  • Goldman JE
  • Berry G
  • Herman B
  • Levine B


Journal of virology

Publication Data

November 5, 1998

Associated Grants

  • Agency: NIA NIH HHS, Id: AG07218
  • Agency: NIAID NIH HHS, Id: AI40246
  • Agency: NIAID NIH HHS, Id: AIO1217

Mesh Terms

  • Alphavirus Infections
  • Amino Acid Sequence
  • Animals
  • Antiviral Agents
  • Apoptosis
  • Apoptosis Regulatory Proteins
  • Chromosomes, Human, Pair 17
  • Encephalitis, Viral
  • Female
  • Genes, bcl-2
  • Humans
  • Male
  • Membrane Proteins
  • Mice
  • Molecular Sequence Data
  • Mutation
  • Proteins
  • Proto-Oncogene Proteins c-bcl-2
  • RNA, Messenger
  • Saccharomyces cerevisiae
  • Sindbis Virus
  • Tissue Distribution
  • Virulence
  • Virus Replication