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PMID: 1731093 Published · ppublish English Comparative Study Journal Article

Extensive sequence-specific information throughout the CAR/RRE, the target sequence of the human immunodeficiency virus type 1 Rev protein.

Journal of virology ·Vol. 66 ·No. 2 ·1992-02-00 ·Pages 1139-51

Dayton ET, Konings DA, Powell DM, Shapiro BA, Butini L, Maizel JV, Dayton AI

Abstract

The significance and location of sequence-specific information in the CAR/RRE, the target sequence for the Rev protein of the human immunodeficiency virus type 1 (HIV-1), have been controversial. We present here a comprehensive experimental and computational approach combining mutational analysis, phylogenetic comparison, and thermodynamic structure calculations with a systematic strategy for distinguishing sequence-specific information from secondary structural information. A target sequence analog was designed to have a secondary structure identical to that of the wild type but a sequence that differs from that of the wild type at every position. This analog was inactive. By exchanging fragments between the wild-type sequence and the inactive analog, we were able to detect an unexpectedly extensive distribution of sequence specificity throughout the CAR/RRE. The analysis enabled us to identify a critically important sequence-specific region, region IIb in the Rev-binding domain, strongly supports a proposed base-pairing interaction in this location, and places forceful constraints on mechanisms of Rev action. The generalized approach presented can be applied to other systems.

Related Genes
gag rev
MeSH Terms
Base Sequence Gene Products, rev/genetics Genes, gag Genes, rev HIV Long Terminal Repeat HIV-1/genetics,physiology Models, Genetic Models, Structural Molecular Sequence Data Mutagenesis, Site-Directed Nucleic Acid Conformation Phylogeny Plasmids Polymerase Chain Reaction Protein Conformation RNA, Viral/genetics,metabolism Virus Replication/genetics rev Gene Products, Human Immunodeficiency Virus
Chemicals
Gene Products, rev RNA, Viral rev Gene Products, Human Immunodeficiency Virus
Authors & Affiliations
7 authors, click to expand affiliations / ORCID
Dayton E T
Laboratory of Immunoregulation, National Institute of Allergy and Infectious Diseases, Bethesda, Maryland 20892.
Konings D A
Powell D M
Shapiro B A
Butini L
Maizel J V
Dayton A I
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Article Info
Journal
Journal of virology
Abbr.
J Virol
ISSN
0022-538X
DOI
10.1128/JVI.66.2.1139-1151.1992
Published
1992-02-00
Pages
1139-51
Language
English
Region
United States
NLM ID
0113724
PMCID
PMC240818
Subset
IM
External Links
PubMed source DOI: 10.1128/JVI.66.2.1139-1151.1992 PMC Full Text View journal details
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