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M94A3302.TXT
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1994-10-25
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Document 3302
DOCN M94A3302
TI Requirement of host factors for HIV-1 Rev function.
DT 9412
AU Shukla RR; Marquis SM; Kimmel PL; Kumar A; Department of Biochemistry &
Molecular Biology, George Washington; University, Washington DC 20037.
SO Int Conf AIDS. 1994 Aug 7-12;10(1):107 (abstract no. PA0047). Unique
Identifier : AIDSLINE ICA10/94369273
AB The nucleocytoplasmic transport of unspliced or singly spliced viral
mRNA transcripts is required for the expression of Human
immunodeficiency virus type 1 structural proteins. HIV-1 regulatory
protein Rev binds to Rev Responsive Element (RRE) in the Env encoding
region of the viral mRNA and facilitates the transport of these
transcripts. Interaction of RRE and Rev is essential but insufficient
for Rev function since deletion of non Rev binding domains of RRE or non
RRE binding domain of Rev results in a significant loss of Rev function.
These observations suggest a requirement of host cell cofactors in Rev
function. Recently we reported the formation of specific RRE RNA-host
nuclear protein RNP complexes in an in vitro RNase protection gel
retardation assay. Non-human cells such as CHO and A9 lack the ability
to form these RNP complexes, however, the presence of human chromosome 6
in A9 cells enabled these cells to form specific RNP complexes
suggesting a role of human cofactor. We have confirmed these in vitro
observations by in vivo analysis of Rev function using a CAT reporter
construct, DM128. The construct DM128 contains CAT gene cloned in the
Env encoding gene 5'to RRE and contains the authentic HIV-1 splice donor
and acceptor sites. We show that mouse-human microcell hybrids
containing human chromosome 6 or 11 support Rev function. These results
demonstrate that human chromosomes 6 and 11 encode host cofactor
required for Rev mediated transport of RRE containing HIV-1 mRNA. Rev
function in the human chromosome 11 containing microcell hybrids
suggests that host factors which interact with Rev or RRE independently
of each other are required for optimal Rev function in vivo.
DE Animal Cell Line Chromosomes, Human, Pair 11 Chromosomes, Human, Pair
6 CHO Cells/METABOLISM/MICROBIOLOGY Gene Products,
rev/*GENETICS/*PHYSIOLOGY Genes, rev Hamsters Human Hybrid
Cells/METABOLISM/MICROBIOLOGY/ULTRASTRUCTURE
HIV-1/*GENETICS/*PHYSIOLOGY In Vitro Ribonucleoproteins/METABOLISM
RNA, Messenger/GENETICS RNA, Viral/GENETICS MEETING ABSTRACT
SOURCE: National Library of Medicine. NOTICE: This material may be
protected by Copyright Law (Title 17, U.S.Code).