Evidence map›Paper›PMID 16948865›Full record

ArticleRetrovirology2006

The virion-associated incoming HIV-1 RNA genome is not targeted by RNA interference.

Ellen M Westerhout, Olivier ter Brake, Ben Berkhout

Abstract read
In one paragraph

Article in Retrovirology, 2006. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 35 papers.

0numbers the graph read from it
0cells of the map it votes in
35citing papers in PubMed
–field-weighted citation impact
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

35 citing papers in PubMed.

  1. Review
  2. Article
  3. CRISPR-Cas13a Inhibits HIV-1 Infection.Molecular therapy. Nucleic acids · 2020
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  19. Review
  20. Toward a durable anti-HIV gene therapy based on RNA interference.Annals of the New York Academy of Sciences · 2009
    Review
4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

3 authors.

Ellen M WesterhoutLaboratory of Experimental Virology, Department of Medical Microbiology, Center for Infection and Immunity Amsterdam (CINIMA), Academic Medical Center, University of Amsterdam, The Netherlands. Westerhout: e.m.westerhout@amc.uva.nl
Olivier ter Brake
Ben Berkhout

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

backgroundRNA interference (RNAi) has proven to be a powerful tool to suppress gene expression and can be used as a therapeutic strategy against human pathogenic viruses such as human immunodeficiency virus type 1 (HIV-1). Theoretically, RNAi-mediated inhibition can occur at two points in the replication cycle, upon viral entry before reverse transcription of the RNA genome, and on the newly transcribed viral RNA transcripts. There have been conflicting results on whether RNAi can target the RNA genome of infecting HIV-1 particles. We have addressed this issue with HIV-1-based lentiviral vectors.

resultsWe determined the transduction efficiency of a lentiviral vector, as measured by GFP expressing cells, which reflects the number of successful integration events in a cell line stably expressing shNef. We did not observe a difference in the transduction efficiency comparing lentiviral vectors with or without the Nef target sequence in their genome. The results were similar with particles pseudotyped with either the VSV-G or HIV-1 envelope. Additionally, no reduced transduction efficiencies were observed with multiple other shRNAs targeting the vector genome or with synthetic siNef when transiently transfected prior to transduction.

conclusionOur findings indicate that the incoming HIV-1 RNA genome is not targeted by RNAi, probably due to inaccessibility to the RNAi machinery. Thus, therapeutic RNAi strategies aimed at preventing proviral integration should be targeting cellular receptors or co-factors involved in pre-integration events.

Indexed as

RNA InterferenceCloning, MolecularGene Products, nefGenetic TherapyGenetic VectorsGenome, ViralGreen Fluorescent ProteinsHIV-1HIV InfectionsHumansLentivirusnef Gene Products, Human Immunodeficiency VirusRNA, Small InterferingRNA, ViralT-LymphocytesTransduction, GeneticGene Products, nefGreen Fluorescent Proteinsnef Gene Products, Human Immunodeficiency VirusRNA, Small InterferingRNA, Viral

Identifiers

PMID16948865
PMCPMC1569866

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Registered trials

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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.