Document 0034
 DOCN  M9470034
 TI    Neurovirulent strains of Alphavirus induce apoptosis in bcl-2-expressing
       cells: role of a single amino acid change in the E2 glycoprotein.
 DT    9409
 AU    Ubol S; Tucker PC; Griffin DE; Hardwick JM; Department of Neurology,
       Johns Hopkins University School of; Medicine, Baltimore, MD 21287.
 SO    Proc Natl Acad Sci U S A. 1994 May 24;91(11):5202-6. Unique Identifier :
       AIDSLINE MED/94255499
 AB    The isolation and sequence comparison of avirulent and neurovirulent
       strains of polio virus, alpha virus, herpes virus, immunodeficiency
       virus, and other viruses have identified genetic changes that are
       required to cause disease in the nervous system. The molecular
       mechanisms by which these genetic changes result in neurovirulence are
       unknown. An avirulent laboratory strain of the Alphavirus Sindbis kills
       most cultured cell lines not by lethal parasitism, but by inducing
       apoptosis or programmed cell death. Transfection of cultured cells with
       the human bcl-2 oncogene can block Sindbis virus-induced apoptosis,
       resulting in a persistent viral infection resembling that observed in
       brains of immunodeficient mice. We investigated the possibility that
       neurovirulent strains of Sindbis virus could overcome the protective
       effects of bcl-2--a potential mechanism to explain the ability of these
       strains to cause fatal disease. Strains of Sindbis virus that were
       lethal for 2- to 4-week-old mice induced apoptotic death in cultured
       cells despite the presence of bcl-2. Using recombinant viruses, we show
       that a single amino acid change in the E2 glycoprotein of Sindbis virus
       confers both neurovirulence and the ability to kill cells expressing
       bcl-2.
 DE    Amino Acid Sequence  Animal  *Apoptosis  Cell Line  Human  Molecular
       Sequence Data  Proto-Oncogene Proteins/BIOSYNTHESIS/*GENETICS  Rats
       Sindbis Virus/GENETICS/METABOLISM/*PATHOGENICITY  Support, Non-U.S.
       Gov't  Support, U.S. Gov't, P.H.S.  Transfection  Tumor Cells, Cultured
       Viral Envelope Proteins/*METABOLISM  Virulence/GENETICS  JOURNAL ARTICLE

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