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PMID: 2833621 Published · ppublish English Journal Article Research Support, U.S. Gov't, P.H.S.

The adeno-associated virus rep gene inhibits replication of an adeno-associated virus/simian virus 40 hybrid genome in cos-7 cells.

Journal of virology ·Vol. 62 ·No. 5 ·1988-05-00 ·Pages 1705-12

Labow MA, Berns KI

Abstract

A hybrid adeno-associated virus (AAV)/simian virus 40 (SV40) genome is described. In this construct SV40 regulatory sequences, including the early promoter/enhancers and origin of DNA replication, were substituted for the AAV p5 promoter, which normally controls expression of the AAV rep gene. The hybrid genome was phenotypically indistinguishable from wild-type AAV in human cells in the presence or absence of helper virus. Upon transfection into cos-7 cells, which constitutively produced the SV40 tumor antigen, the genome replicated as a plasmid when the SV40 origin was used, although with a low efficiency compared with that of a non-AAV/SV40 replicon. The low level of replication was due to an inhibitory effect of an AAV rep gene product and was specific for replicons containing AAV sequences. Target AAV sequences required for inhibition by rep appeared to reside in the terminal repetitions since deletion of these sequences allowed efficient replication in the presence of the rep gene. The possible role for negative autoregulation of AAV DNA replication in latent infection and helper-dependent replication by AAV is discussed.

MeSH Terms
Adenoviridae/genetics,physiology Animals Cell Line Chimera Chromosome Deletion DNA Replication DNA, Viral/biosynthesis Genes, Viral Humans Mutation Plasmids RNA, Viral/analysis Simian virus 40/genetics,physiology Transfection Virus Replication
Chemicals
DNA, Viral RNA, Viral
Authors & Affiliations
2 authors, click to expand affiliations / ORCID
Labow M A
Department of Molecular Biology, Princeton University, New Jersey 08544.
Berns K I
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Article Info
Journal
Journal of virology
Abbr.
J Virol
ISSN
0022-538X
DOI
10.1128/JVI.62.5.1705-1712.1988
Published
1988-05-00
Pages
1705-12
Language
English
Region
United States
NLM ID
0113724
PMCID
PMC253208
Subset
IM
Grants
NIAID NIH HHS · AI 22251 · United States
External Links
PubMed source DOI: 10.1128/JVI.62.5.1705-1712.1988 PMC Full Text View journal details
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