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M9470034.TXT
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1994-07-02
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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
SOURCE: National Library of Medicine. NOTICE: This material may be
protected by Copyright Law (Title 17, U.S.Code).