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M9640608.TXT
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1996-03-04
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Document 0608
DOCN M9640608
TI Inhibition of human immunodeficiency virus type 1 and vaccinia virus
infection by a dominant negative factor of the interferon regulatory
factor family expressed in monocytic cells.
DT 9604
AU Thornton AM; Buller RM; DeVico AL; Wang IM; Ozato K; Laboratory of
Molecular Growth Regulation, National Institute of; Child Health and
Human Development, National Institutes of; Health, Bethesda, MD 20892,
USA.
SO Proc Natl Acad Sci U S A. 1996 Jan 9;93(1):383-7. Unique Identifier :
AIDSLINE MED/96133941
AB ICSBP is a member of the interferon (IFN) regulatory factor (IRF) family
that regulates expression of type I interferon (IFN) and IFN-regulated
genes. To study the role of the IRF family in viral infection, a cDNA
for the DNA-binding domain (DBD) of ICSBP was stably transfected into
U937 human monocytic cells. Clones that expressed DBD exhibited a
dominant negative phenotype and did not elicit antiviral activity
against vesicular stomatitis virus (VSV) infection upon IFN treatment.
Most notably, cells expressing DBD were refractory to infection by
vaccinia virus (VV) and human immunodeficiency virus type 1 (HIV-1). The
inhibition of VV infection was attributed to defective virion assembly,
and that of HIV-1 to low CD4 expression and inhibition of viral
transcription in DBD clones. HIV-1 and VV were found to have sequences
in their regulatory regions similar to the IFN-stimulated response
element (ISRE) to which IRF family proteins bind. Accordingly, these
viral sequences and a cellular ISRE bound a shared factor(s) expressed
in U937 cells. These observations suggest a novel host-virus
relationship in which the productive infection of some viruses is
regulated by the IRF-dependent transcription pathway through the ISRE.
DE Base Sequence Carrier Proteins/*PHYSIOLOGY Cells, Cultured
DNA-Binding Proteins/METABOLISM *Gene Expression Regulation, Viral
Genes, Dominant Human HIV Infections/*PREVENTION & CONTROL
HIV-1/*GENETICS Interferons/PHYSIOLOGY Molecular Sequence Data
Oligodeoxyribonucleotides/CHEMISTRY Regulatory Sequences, Nucleic Acid
Repressor Proteins/*GENETICS/METABOLISM Vaccinia/*PREVENTION & CONTROL
Vaccinia Virus/*GENETICS JOURNAL ARTICLE
SOURCE: National Library of Medicine. NOTICE: This material may be
protected by Copyright Law (Title 17, U.S.Code).