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PMID: 8013464 Published · ppublish English Journal Article Research Support, Non-U.S. Gov't

Evolution of a disrupted TAR RNA hairpin structure in the HIV-1 virus.

The EMBO journal ·Vol. 13 ·No. 11 ·1994-06-01 ·Pages 2650-9

Klaver B, Berkhout B

Abstract

Human immunodeficiency virus type 1 (HIV-1) RNA contains an extended hairpin structure at the 5' end (the TAR element) that is essential for viral replication. The upper part of the stem-loop structure binds the virally encoded transcriptional activator protein Tat and cellular co-factors, but no clear function for the lower stem region has been established. Here, we report that mutant HIV-1 viruses with base substitutions in the lower stem region are dead, most likely at the level of transcription from an integrated provirus. By using large amounts of these mutant DNA constructs for transfections, revertant viruses with a great variety of genetic changes (point mutations, short deletions) could be isolated in prolonged culture experiments that lasted over 6 months. The pattern and evolution of these changes supported the notion that base-pairing of the lower stem region is essential for optimal HIV-1 replication. The functional and genetic plasticities of this RNA domain and the HIV-1 long terminal repeat promoter are discussed.

MeSH Terms
Base Composition Base Sequence Biological Evolution Cell Line DNA Mutational Analysis DNA, Viral/genetics HIV Long Terminal Repeat/genetics HIV-1/genetics,growth & development,physiology Humans Kinetics Molecular Sequence Data Nucleic Acid Conformation Point Mutation/genetics Proviruses RNA, Viral/analysis,chemistry Transcription, Genetic Virus Replication/genetics
Chemicals
DNA, Viral RNA, Viral
Authors & Affiliations
2 authors, click to expand affiliations / ORCID
Klaver B
University of Amsterdam, Department of Virology, Academic Medical Center, The Netherlands.
Berkhout B
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Article Info
Journal
The EMBO journal
Abbr.
EMBO J
ISSN
0261-4189
Published
1994-06-01
Pages
2650-9
Language
English
Region
England
NLM ID
8208664
PMCID
PMC395139
Subset
IM
External Links
PubMed source PMC Full Text View journal details
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