Evidence map›Paper›PMID 12805416›Full record

ArticleJournal of virology2003

Sustained small interfering RNA-mediated human immunodeficiency virus type 1 inhibition in primary macrophages.

Erwei Song, Sang-Kyung Lee, Derek M Dykxhoorn, Carl Novina, Dong Zhang, Keith Crawford, Jan Cerny, Phillip A Sharp, Judy Lieberman, N Manjunath and 1 more

Erratum issuedOpen access · greenAbstract read
In one paragraph

Article in Journal of virology, 2003. The graph could read no effect estimate from its abstract, so it casts no vote on the map. An erratum has been issued. Cited by 103 papers.

0numbers the graph read from it
0cells of the map it votes in
103citing papers in PubMed
8.7field-weighted citation impact, top 1% 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

103 citing papers in PubMed, 230 citations in OpenAlex.

  1. Non-coding RNAs and neuroinflammation: implications for neurological disorders.Experimental biology and medicine (Maywood, N.J.) · 2024
    Review
  2. Article
  3. HCV and tumor-initiating stem-like cells.Frontiers in physiology · 2022
    Review
  4. Review
  5. Article
  6. Article
  7. Article
  8. Article
  9. Article
  10. Article
  11. Review
  12. Review
  13. Article
  14. The panorama of miRNA-mediated mechanisms in mammalian cells.Cellular and molecular life sciences : CMLS · 2014
    Review
  15. Design of nanodrugs for miRNA targeting in tumor cells.Journal of biomedical nanotechnology · 2014
    Article
  16. Drosha as an interferon-independent antiviral factor.Proceedings of the National Academy of Sciences of the United States of America · 2014
    Article
  17. Article
  18. The macrophage: a therapeutic target in HIV-1 infection.Molecular and cellular therapies · 2014
    Review
  19. Review
  20. Diversifying microRNA sequence and function.Nature reviews. Molecular cell biology · 2013
    Review

43 more citing papers are in PubMed but not listed here.

4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

11 authors at 4 institutions in 1 country.

Erwei SongCenter for Blood Research, Harvard Medical School, Boston, Massachusetts 02115, USA.
Sang-Kyung Lee
Derek M Dykxhoorn
Carl Novina
Dong Zhang
Keith Crawford
Jan Cerny
Phillip A Sharp
Judy Lieberman
N Manjunath
Premlata Shankar
Dana-Farber/Boston Children's Cancer and Blood Disorders Center · USHarvard University · USCenter for Cancer Research · USMassachusetts Institute of Technology · US

Funding

CD8 T CELL DYSFUNCTION IN HIV INFECTIONR01AI042519 · NIAID · IMMUNE DISEASE INSTITUTE, INC. · PI LIEBERMAN, JUDY · 1998 to 2005
$2.2M
REGULATION OF MRNA PROCESSINGR37GM034277 · NIGMS · MASSACHUSETTS INSTITUTE OF TECHNOLOGY · PI SHARP, PHILLIP A · 1995 to 2004
$2.1M
ROLE OF FUCOSYLTRANSFERASE IN ANTIVIRAL CYTOTOXICITYR01AI046566 · NIAID · IMMUNE DISEASE INSTITUTE, INC. · PI SWAMY, MANJUNATH NARASIMHA · 2000 to 2004
$2.0M
EFFECTOR/MEMORY CD8 T CELL FUNCTIONS IN HIV INFECTIONR21AI049792 · NIAID · IMMUNE DISEASE INSTITUTE, INC. · PI SHANKAR, PREMLATA · 2001 to 2001
$426k
CTL LYSIS OF HIV-INFECTED CD4 T CELLS AND MACROPHAGESR21AI045306 · NIAID · IMMUNE DISEASE INSTITUTE, INC. · PI SHANKAR, PREMLATA · 1999 to 2000
$284k
ROLE OF FUCOSYLTRANSEFERASE IN ANTIVIRAL CYTOTOXICITYR21AI046566 · NIAID · IMMUNE DISEASE INSTITUTE, INC. · PI SWAMY, MANJUNATH NARASIMHA · 2000 to 2000
$141k
A B-CELL SPECIFIC COFACTOR OF NUCLEOSOME REMODELINGF32AI010523 · NIAID · MASSACHUSETTS INSTITUTE OF TECHNOLOGY · PI NOVINA, CARL D · 2000 to 2002
$128k
NIAID NIH HHS AI42519NIAID NIH HHS AI45306NIAID NIH HHS AI46566NIAID NIH HHS AI49792NIAID NIH HHS F32 AI010523NIAID NIH HHS F32-AI10523NIAID NIH HHS R01 AI042519NIAID NIH HHS R01 AI046566NIAID NIH HHS R21 AI046566NIGMS NIH HHS R37 GM034277NIGMS NIH HHS R37-GM34277PHS HHS P01-42063
6 · The paper itself

Abstract

Small interfering RNAs (siRNAs) can induce potent gene silencing by degradation of cognate mRNA. However, in dividing cells, the silencing lasts only 3 to 7 days, presumably because of siRNA dilution with cell division. Here, we investigated if sustained siRNA-mediated silencing of human immunodeficiency virus type 1 (HIV-1) is possible in terminally differentiated macrophages, which constitute an important reservoir of HIV in vivo. CCR5, the major HIV-1 coreceptor in macrophages, and the viral structural gene for p24 were targeted either singly or in combination. When transfected 2 days prior to infection, both CCR5 and p24 siRNAs effectively reduced HIV-1 infection for the entire 15-day period of observation, and combined targeting of both genes abolished infection. To investigate whether exogenously introduced siRNA is maintained stably in macrophages, we tested the kinetics of siRNA-mediated viral inhibition by initiating infections at various times (2 to 15 days) after transfection with CCR5 and p24 siRNAs. HIV suppression mediated by viral p24 siRNA progressively decreased and was lost by day 7 posttransfection. In contrast, viral inhibition by cellular CCR5 knockdown was sustained even when transfection preceded infection by 15 days, suggesting that the continued presence of target RNA may be needed for persistence of siRNA. The longer sustenance of CCR5 relative to p24 siRNA in uninfected macrophages was also confirmed by detection of internalized siRNA by modified Northern blot analysis. We also tested the potential of p24 siRNA to stably silence HIV in the setting of an established infection where the viral target gene is actively transcribed. Under these circumstances, long-term suppression of HIV replication could be achieved with p24 siRNA. Thus, siRNAs can induce potent and long-lasting HIV inhibition in nondividing cells such as macrophages.

Indexed as

Gene SilencingAntiviral AgentsBase SequenceDNA PrimersHIV-1HIV Core Protein p24HumansMacrophagesReceptors, CCR5RNA, Small InterferingVirus ReplicationAntiviral AgentsDNA PrimersHIV Core Protein p24Receptors, CCR5RNA, Small Interfering

Identifiers

PMID12805416
PMCPMC164789
OpenAlexW2108330459

What OpenQuestion holds

Textmetadata
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.