Evidence map›Paper›PMID 29954456›Full record

ArticleRetrovirology2018

The RNA surveillance proteins UPF1, UPF2 and SMG6 affect HIV-1 reactivation at a post-transcriptional level.

Shringar Rao, Raquel Amorim, Meijuan Niu, Abdelkrim Temzi, Andrew J Mouland

Open access · goldAbstract read
In one paragraph

Article in Retrovirology, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 25 papers.

0numbers the graph read from it
0cells of the map it votes in
25citing papers in PubMed
2.2field-weighted citation impact, top 13% of its field
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

25 citing papers in PubMed, 37 citations in OpenAlex.

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  15. HibeRNAtion: HIV-1 RNA Metabolism and Viral Latency.Frontiers in cellular and infection microbiology · 2022
    Review
  16. Article
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  18. Article
  19. RNA Flow Cytometry for the Study of T Cell Metabolism.International journal of molecular sciences · 2021
    Review
  20. Article
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

5 authors at 2 institutions in 1 country.

Shringar RaoHIV-1 RNA Trafficking Laboratory, Lady Davis Institute at the Jewish General Hospital, Montreal, QC, H3T 1E2, Canada.
Raquel AmorimHIV-1 RNA Trafficking Laboratory, Lady Davis Institute at the Jewish General Hospital, Montreal, QC, H3T 1E2, Canada.
Meijuan NiuHIV-1 RNA Trafficking Laboratory, Lady Davis Institute at the Jewish General Hospital, Montreal, QC, H3T 1E2, Canada.
Abdelkrim TemziHIV-1 RNA Trafficking Laboratory, Lady Davis Institute at the Jewish General Hospital, Montreal, QC, H3T 1E2, Canada.
Andrew J MoulandHIV-1 RNA Trafficking Laboratory, Lady Davis Institute at the Jewish General Hospital, Montreal, QC, H3T 1E2, Canada. andrew.mouland@mcgill.ca.
Jewish General Hospital · CAMcGill University · CA

Funding

Institute of Infection and Immunity HIG-133050
6 · The paper itself

Abstract

backgroundThe ability of human immunodeficiency virus type 1 (HIV-1) to form a stable viral reservoir is the major obstacle to an HIV-1 cure and post-transcriptional events contribute to the maintenance of viral latency. RNA surveillance proteins such as UPF1, UPF2 and SMG6 affect RNA stability and metabolism. In our previous work, we demonstrated that UPF1 stabilises HIV-1 genomic RNA (vRNA) and enhances its translatability in the cytoplasm. Thus, in this work we evaluated the influence of RNA surveillance proteins on vRNA expression and, as a consequence, viral reactivation in cells of the lymphoid lineage.

methodsQuantitative fluorescence in situ hybridisation-flow cytometry (FISH-flow), si/shRNA-mediated depletions and Western blotting were used to characterise the roles of RNA surveillance proteins on HIV-1 reactivation in a latently infected model T cell line and primary CD4+ T cells.

resultsUPF1 was found to be a positive regulator of viral reactivation, with a depletion of UPF1 resulting in impaired vRNA expression and viral reactivation. UPF1 overexpression also modestly enhanced vRNA expression and its ATPase activity and N-terminal domain were necessary for this effect. UPF2 and SMG6 were found to negatively influence viral reactivation, both via an interaction with UPF1. UPF1 knockdown also resulted in reduced vRNA levels and viral gene expression in HIV-1-infected primary CD4+ T cells.

conclusionOverall, these data suggest that RNA surveillance proteins affect HIV-1 gene expression at a post-transcriptional level. An elucidation of the role of vRNA metabolism on the maintenance of HIV-1 persistence can lead to the development of novel curative strategies.

Indexed as

Gene Expression Regulation, ViralVirus ActivationCD4-Positive T-LymphocytesCell LineEndoribonucleasesFlow CytometryGene ExpressionGene Knockdown TechniquesGenome, ViralHIV-1HIV InfectionsHost-Pathogen InteractionsHumansProtein BindingProvirusesRNA-Binding ProteinsEndoribonucleasesRNA-Binding ProteinsRNA HelicasesRNA, ViralSMG6 protein, humanTelomeraseTrans-ActivatorsTranscription FactorsUPF1 protein, humanUPF2 protein, humanHIV-1 genomic RNA stabilityHIV-1 latencyNMDNonsense-mediated mRNA decayPost-transcriptional regulationRNA surveillance proteinsSMG6UPF1UPF2

Identifiers

PMID29954456
PMCPMC6022449
OpenAlexW2809808840

What OpenQuestion holds

Textmetadata
LicenceCC BY
Read underepoch 390

Registered trials

None linked

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.