• Register
X
Forgot Password

If you have forgotten your password you can enter your email here and get a temporary password sent to your email.

X

Leaving Community

Are you sure you want to leave this community? Leaving the community will revoke any permissions you have been granted in this community.

No
Yes

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

Authors

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

Journal

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