Evidence map›Paper›PMID 35299788›Full record

ArticleVirus evolution2021

Analyses of HIV proteases variants at the threshold of viability reveals relationships between processing efficiency and fitness.

Gily Schneider-Nachum, Julia Flynn, David Mavor, Celia A Schiffer, Daniel N A Bolon

Abstract read
In one paragraph

Article in Virus evolution, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 5 papers.

0numbers the graph read from it
0cells of the map it votes in
5citing 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

5 citing papers in PubMed.

  1. Article
  2. Article
  3. Contributions of Hyperactive Mutations in MACS infectious diseases · 2024
    Article
  4. Article
  5. 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.

Gily Schneider-NachumDepartment of Biochemistry and Molecular Pharmacology, University of Massachusetts Medical School, 364 Plantation St, Worcester, MA 01605, USA.
Julia FlynnDepartment of Biochemistry and Molecular Pharmacology, University of Massachusetts Medical School, 364 Plantation St, Worcester, MA 01605, USA.
David MavorDepartment of Biochemistry and Molecular Pharmacology, University of Massachusetts Medical School, 364 Plantation St, Worcester, MA 01605, USA.
Celia A SchifferDepartment of Biochemistry and Molecular Pharmacology, University of Massachusetts Medical School, 364 Plantation St, Worcester, MA 01605, USA.
Daniel N A BolonDepartment of Biochemistry and Molecular Pharmacology, University of Massachusetts Medical School, 364 Plantation St, Worcester, MA 01605, USA.ORCID https://orcid.org/0000-0001-5857-6676

Funding

Relating protein interaction networks to physiology by systematic mutant analysesR01GM112844 · NIGMS · UNIV OF MASSACHUSETTS MED SCH WORCESTER · PI BOLON, DANIEL N · 2015 to 2023
$2.7M
Integration of Evolution to Avoid Resistance in Structure Based Drug DesignR01GM135919 · NIGMS · UNIV OF MASSACHUSETTS MED SCH WORCESTER · PI SCHIFFER, CELIA A. · 2020 to 2023
$2.5M
Investigating structure activity relationships in autoprocessing by HIV-1 proteaseR21AI157871 · NIAID · UNIV OF MASSACHUSETTS MED SCH WORCESTER · PI BOLON, DANIEL N · 2021 to 2022
$461k
NIAID NIH HHS R21 AI157871NIGMS NIH HHS R01 GM112844NIGMS NIH HHS R01 GM135919
6 · The paper itself

Abstract

Investigating the relationships between protein function and fitness provides keys for understanding biochemical mechanisms that underly evolution. Mutations with partial fitness defects can delineate the threshold of biochemical function required for viability. We utilized a previous deep mutational scan of HIV-1 protease (PR) to identify variants with 15-45 per cent defects in replication and analysed the biochemical function of eight variants (L10M, L10S, V32C, V32I, A71V, A71S, Q92I, Q92N). We purified each variant and assessed the efficiency of peptide cleavage for three cut sites (MA-CA, TF-PR, and PR-RT) as well as gel-based analyses of processing of purified Gag. The cutting activity of at least one site was perturbed relative to WT protease for all variants, consistent with cutting activity being a primary determinant of fitness effects. We examined the correlation of fitness defects with cutting activity of different sites. MA-CA showed the weakest correlation (

Indexed as

HIV-1 proteasemulti-functionalselection pressure

Identifiers

PMID35299788
PMCPMC8923237

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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.