About: Trans-inhibition of HIV-1 by a long hairpin RNA expressed within the viral genome

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An Entity of Type : schema:ScholarlyArticle, within Data Space : covidontheweb.inria.fr associated with source document(s)

Attributes	Values
type	Academic Article research paper schema:ScholarlyArticle
isDefinedBy	Covid-on-the-Web dataset
has title	Trans-inhibition of HIV-1 by a long hairpin RNA expressed within the viral genome
Creator	Berkhout, Ben Haasnoot, Joost Konstantinova, Pavlina De Haan, Peter Olivier Ter Brake,
Source	Medline; PMC
abstract	BACKGROUND: Human immunodeficiency virus type 1 (HIV-1) can be inhibited by means of RNA silencing or interference (RNAi) using synthetic short interfering RNAs (siRNAs) or gene constructs encoding short hairpin RNAs (shRNAs) or long hairpin RNAs (lhRNAs). The use of siRNA and shRNA as antiviral therapeutic is limited because of the emergence of viral escape mutants. This problem is theoretically prevented by intracellular expression of lhRNAs generating multiple siRNAs that target the virus simultaneously, thus reducing the chance of viral escape. However, gene constructs encoding lhRNA molecules face problems with delivery to the right cells in an infected individual. In order to solve this problem, we constructed an HIV-1 variant with a 300 bp long hairpin structure in the 3' part of the genome corresponding to the Nef gene (HIV-lhNef). RESULTS: Intriguingly, HIV-lhNef potently inhibited wild-type HIV-1 production in trans. However, HIV-lhNef demonstrated a severe production and replication defect, which we were able to solve by selecting spontaneous virus variants with truncated hairpin structures. Although these escape variants lost the ability to trans-inhibit HIV-1, they effectively outgrew the wild-type virus in competition experiments in SupT1 cells. CONCLUSION: Expression of the lhNef hairpin within the HIV-1 genome results in potent trans-inhibition of wild-type HIV-1. Although the mechanism of trans-inhibition is currently unknown, it remains of interest to study the molecular details because the observed effect is extremely potent. This may have implications for the development of virus strains to be used as live-attenuated virus vaccines.
has issue date	2007-03-01(xsd:dateTime)
bibo:doi	10.1186/1742-4690-4-15
bibo:pmid	17331227
has license	cc-by
sha1sum (hex)	2c4528b1cf4a44cba63268ee2a4d20370626ba87
schema:url	https://doi.org/10.1186/1742-4690-4-15
resource representing a document's title	Trans-inhibition of HIV-1 by a long hairpin RNA expressed within the viral genome
has PubMed Central identifier	PMC1819390
has PubMed identifier	17331227
schema:publication	Retrovirology
resource representing a document's body	covid:2c4528b1cf4a44cba63268ee2a4d20370626ba87#body_text
is schema:about of	named entity 'therapeutic' named entity 'simultaneously' named entity 'reducing' named entity 'gene' named entity 'gene' named entity 'HIV-1' named entity 'hairpin' named entity 'individual' named entity 'hairpin structure' named entity 'target' named entity 'RNAs' named entity 'HIV-1' named entity 'siRNA' named entity 'viral genome' named entity 'Roche' named entity 'HIV-1' named entity 'agarose gel electrophoresis' named entity 'HIV-1' named entity 'wild-type' named entity 'transfected' named entity 'wild-type' named entity 'RNAi' named entity 'Vpr' named entity 'HIV-1' named entity 'HBV' named entity 'HIV-1' named entity 'siRNAs' named entity 'PBS' named entity 'siRNAs' named entity 'phenotypic' named entity 'Peripheral blood mononuclear cells' named entity 'PCR' named entity 'human immunodeficiency virus type 1' named entity 'virus replication' named entity '1, 2' named entity 'macaques' named entity 'antiviral' named entity 'deletions' named entity 'CMV promoter' named entity 'HIV' named entity 'MLV' named entity 'HIV-1' named entity 'HIV' named entity 'HIV-1' named entity 'Nef protein' named entity 'luciferase' named entity 'HIV-1' named entity 'transfection' named entity 'virus' named entity 'complementarity' named entity 'supernatant' named entity 'culture medium' named entity 'RNAi' named entity 'IFN' named entity 'hairpin structure' named entity 'Invitrogen' named entity 'HIV-1' named entity 'phenotype' named entity 'time-point' named entity 'cell lines' named entity 'IL-2' named entity 'RNAi' named entity 'HIV' named entity 'internal control' named entity 'wild-type virus' named entity 'HIV' named entity 'kidney' named entity 'plasmid' named entity 'inverted repeat' named entity 'HIV-1' named entity 'HIV' named entity 'IFN' named entity 'Plasmid' named entity 'shRNAs' named entity 'Vpx' named entity 'HIV-1' named entity 'gene'

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