Evidence map›Paper›PMID 34702287›Full record

ArticleAIDS research and therapy2021

Ribonuclease zymogen induces cytotoxicity upon HIV-1 infection.

Ian W Windsor, Dawn M Dudley, David H O'Connor, Ronald T Raines

Open access · goldAbstract read
In one paragraph

Article in AIDS research and therapy, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 2 papers.

0numbers the graph read from it
0cells of the map it votes in
2citing papers in PubMed
0.1field-weighted citation impact, top 54% 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

2 citing papers in PubMed, 1 citations in OpenAlex.

  1. Reductive Methylation: An Alternative to Lysine → Arginine Mutagenesis.Journal of peptide science : an official publication of the European Peptide Society · 2026
    Article
  2. Emerging biological functions of ribonuclease 1 and angiogenin.Critical reviews in biochemistry and molecular biology · 2022
    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

4 authors at 2 institutions in 1 country.

Ian W WindsorDepartment of Chemistry, Massachusetts Institute of Technology, Cambridge, MA, 02139, USA.ORCID 0000-0002-6289-6928
Dawn M DudleyDepartment of Pathology and Laboratory Medicine, University of Wisconsin-Madison, Madison, WI, 53706, USA.
David H O'ConnorDepartment of Pathology and Laboratory Medicine, University of Wisconsin-Madison, Madison, WI, 53706, USA.
Ronald T RainesDepartment of Chemistry, Massachusetts Institute of Technology, Cambridge, MA, 02139, USA. rtraines@mit.edu.ORCID 0000-0001-7164-1719
University of Wisconsin–Madison · USBoston Children's Hospital · US

Funding

VIRUS PRODUCTION COREP30CA014051 · NCI · MASSACHUSETTS INSTITUTE OF TECHNOLOGY · PI Paula T Hammond · 1985 to 2026
$93.9M
Zika virus pathophysiology during pregnancyP01AI132132 · NIAID · UNIVERSITY OF WISCONSIN-MADISON · PI O'CONNOR, DAVID H. · 2018 to 2022
$10.2M
RIBONUCLEASES IN CANCER THERAPYR01CA073808 · NCI · UNIVERSITY OF WISCONSIN-MADISON · PI RAINES, RONALD T · 1997 to 2024
$7.3M
STRUCTURE--FUNCTION ANALYSIS OF RIBONUCLEASE AR01GM044783 · NIGMS · UNIVERSITY OF WISCONSIN-MADISON · PI RAINES, RONALD T · 1990 to 2021
$7.1M
NCI NIH HHS P30 CA014051NCI NIH HHS R01 CA073808NIAID NIH HHS P01 AI132132NIGMS NIH HHS R01 GM044783
6 · The paper itself

Abstract

backgroundTargeting RNA is a promising yet underdeveloped modality for the selective killing of cells infected with HIV-1. The secretory ribonucleases (RNases) found in vertebrates have cytotoxic ribonucleolytic activity that is kept in check by a cytosolic ribonuclease inhibitor protein, RI.

methodsWe engineered amino acid substitutions that enable human RNase 1 to evade RI upon its cyclization into a zymogen that is activated by the HIV-1 protease. In effect, the zymogen has an HIV-1 protease cleavage site between the termini of the wild-type enzyme, thereby positioning a cleavable linker over the active site that blocks access to a substrate.

resultsThe amino acid substitutions in RNase 1 diminish its affinity for RI by 10

conclusionsThese data demonstrate the utility of ribonuclease zymogens as biologic prodrugs.

Indexed as

HIV-1HIV InfectionsAnimalsEnzyme PrecursorsHumansModels, MolecularRibonucleasesEnzyme PrecursorsRibonucleases

Identifiers

PMID34702287
PMCPMC8549155
OpenAlexW3208203267

What OpenQuestion holds

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LicenceCC BY
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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.