Evidence map›Paper›PMID 9261367›Full record

ArticleJournal of virology1997

Inhibition of human immunodeficiency virus type 1 replication in vitro by a novel combination of anti-Tat single-chain intrabodies and NF-kappa B antagonists.

A M Mhashilkar, D K Biswas, J LaVecchio, A B Pardee, W A Marasco

Open access · bronzeAbstract read
In one paragraph

Article in Journal of virology, 1997. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 17 papers.

0numbers the graph read from it
0cells of the map it votes in
17citing papers in PubMed
2.5field-weighted citation impact, top 9% 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

17 citing papers in PubMed, 62 citations in OpenAlex.

  1. Review
  2. Applying Antibodies Inside Cells: Principles and Recent Advances in Neurobiology, Virology and Oncology.BioDrugs : clinical immunotherapeutics, biopharmaceuticals and gene therapy · 2020
    Review
  3. CD71mBio · 2019
    Article
  4. Review
  5. Article
  6. Article
  7. Article
  8. Article
  9. Review
  10. Article
  11. Article
  12. Article
  13. Article
  14. Generation of recombinant antibodies.Molecular biotechnology · 1999
    Review
  15. Nitric oxide inhibits HIV tat-induced NF-kappaB activation.The American journal of pathology · 1999
    Article
  16. Gene therapy for HIV infections: Intracellular immunization.The Canadian journal of infectious diseases = Journal canadien des maladies infectieuses · 1999
    Article
  17. 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

5 authors at 1 institution in 1 country.

A M MhashilkarDivision of Human Retrovirology, Dana-Farber Cancer Institute, Boston, Massachusetts 02115, USA.
D K Biswas
J LaVecchio
A B Pardee
W A Marasco
Dana-Farber Cancer Institute · US

Funding

VectorP30CA006516 · NCI · DANA-FARBER CANCER INSTITUTE · PI A. Heather Eliassen · 1985 to 2026
$330.6M
DFCI-BIDMC-CH CENTER FOR AIDS RESEARCHP30AI028691 · NIAID · DANA-FARBER CANCER INSTITUTE · PI SODROSKI, JOSEPH G · 1989 to 2003
$6.2M
MECHANISM OF ACTION OF THE TAT PRODUCT OF HIV-1R01AI028785 · NIAID · DANA-FARBER CANCER INSTITUTE · PI MARASCO, WAYNE A. · 1989 to 2002
$637k
NCI NIH HHS P30 CA06516NIAID NIH HHS AI28785NIAID NIH HHS P30 AI28691
6 · The paper itself

Abstract

Human immunodeficiency virus type 1 (HIV-1) Tat, an early regulatory protein that is critical for viral gene expression and replication, transactivates the HIV-1 long terminal repeat (LTR) via its binding to the transactivation response element (TAR) and, along with other cellular factors, increases viral transcription initiation and elongation. Tat also superactivates the HIV-1 promoter through a TAR-independent mechanism, including tumor necrosis factor alpha-induced and protein kinase C (PKC)-dependent activation of NF-kappa B, and inhibitors of Tat and NF-kappa B cooperatively down-regulate this Tat-mediated LTR superactivation. In this study, a combined pharmacologic and genetic strategy using two PKC (NF-kappa B) inhibitors, pentoxifylline (PTX) and Gö-6976, and a stably expressed anti-Tat single-chain intracellular antibody (sFv intrabody) was employed to obtain cooperative inhibition of both HIV-1 LTR-driven gene expression and HIV-1 replication. Treatment of cells with PTX and Gö-6976 resulted in cooperative inhibition of both HIV-1 LTR-driven gene expression and HIV-1 replication. In addition, the combined use of anti-Tat sFv intrabodies and the two NF-kappa B inhibitors retained the virus in the latent state for as long as 45 days. The combined treatment resulted in more durable inhibition of HIV-1 replication than was seen with the NF-kappa B inhibitors alone or the anti-Tat sFv intrabodies alone. Together, these results suggest that in future clinical gene therapy trials, a combined pharmacologic and genetic strategy like the one reported here may improve the survival of transduced cells and prolong clinical benefit.

Indexed as

PyrrolesAnti-HIV AgentsBenzodiazepinesCarbazolesCD4-Positive T-LymphocytesCell LineGene Products, tatHIV-1HIV AntibodiesHIV Long Terminal RepeatHumansIndolesJurkat CellsLeukocytes, MononuclearNF-kappa BPentoxifyllineAnti-HIV AgentsBenzodiazepinesCarbazolesGene Products, tatGo 6976HIV AntibodiesIndolesNF-kappa BPentoxifyllinePhytohemagglutininsPyrrolesRo 24-7429tat Gene Products, Human Immunodeficiency VirusTumor Necrosis Factor-alpha

Identifiers

PMID9261367
PMCPMC191923
OpenAlexW1913352947

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.