Evidence map›Paper›PMID 33142846›Full record

ArticleViruses2020

A Mutated PB1 Residue 319 Synergizes with the PB2 N265S Mutation of the Live Attenuated Influenza Vaccine to Convey Temperature Sensitivity.

Andrew Cox, Jordana Schmierer, Josephine D'Angelo, Andrew Smith, Dustyn Levenson, John Treanor, Baek Kim, Stephen Dewhurst

Open access · goldAbstract read
In one paragraph

Article in Viruses, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 4 papers.

0numbers the graph read from it
0cells of the map it votes in
4citing papers in PubMed
0.4field-weighted citation impact, top 34% 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

4 citing papers in PubMed, 5 citations in OpenAlex.

  1. Review
  2. Article
  3. Article
  4. 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

8 authors at 6 institutions in 1 country.

Andrew CoxDepartment of Microbiology and Immunology, University of Rochester School of Medicine and Dentistry, Rochester, New York, NY 14642, USA.ORCID 0000-0003-3485-8892
Jordana SchmiererDepartment of Microbiology and Immunology, University of Rochester School of Medicine and Dentistry, Rochester, New York, NY 14642, USA.
Josephine D'AngeloDepartment of Microbiology and Immunology, University of Rochester School of Medicine and Dentistry, Rochester, New York, NY 14642, USA.ORCID 0000-0003-1278-4925
Andrew SmithDepartment of Microbiology and Immunology, University of Rochester School of Medicine and Dentistry, Rochester, New York, NY 14642, USA.
Dustyn LevensonDepartment of Microbiology and Immunology, University of Rochester School of Medicine and Dentistry, Rochester, New York, NY 14642, USA.ORCID 0000-0002-5994-7341
John TreanorDepartment of Microbiology and Immunology, University of Rochester School of Medicine and Dentistry, Rochester, New York, NY 14642, USA.
Baek KimDepartment of Microbiology and Immunology, University of Rochester School of Medicine and Dentistry, Rochester, New York, NY 14642, USA.
Stephen DewhurstDepartment of Microbiology and Immunology, University of Rochester School of Medicine and Dentistry, Rochester, New York, NY 14642, USA.
University of Rochester · USBiomedical Advanced Research and Development Authority · USCincinnati Children's Hospital Medical Center · USEmory University · USSUNY Upstate Medical University · USWayne State University · US

Funding

The T32 Predoctoral Training Program in Immunology (PTPI)T32AI007285 · NIAID · UNIVERSITY OF ROCHESTER · PI Scott Andrew Gerber, JACQUES Robert · 1986 to 2026
$7.6M
Medical Scientist Training ProgramT32GM063483 · NIGMS · UNIVERSITY OF CINCINNATI · PI KHURANA HERSHEY, GURJIT K. · 2002 to 2022
$6.7M
Training in Cellular, Biochemical and Molecular SciencesT32GM068411 · NIGMS · UNIVERSITY OF ROCHESTER · PI MAQUAT, LYNNE E · 2005 to 2019
$3.9M
Infection and Immunity: The Pathogenesis of Host-Microbe InteractionsT32AI118689 · NIAID · UNIVERSITY OF ROCHESTER · PI Paul M. Dunman, BRIAN M WARD · 2015 to 2026
$2.5M
Pathogenesis and therapeutic targeting of immune disordersT32AI118697 · NIAID · CINCINNATI CHILDRENS HOSP MED CTR · PI HILDEMAN, DAVID A · 2016 to 2020
$683k
Enhanced Live Attenuated Influenza Virus With Improved Safety and ImmunogenicityR21AI112717 · NIAID · UNIVERSITY OF ROCHESTER · PI DEWHURST, STEPHEN · 2014 to 2015
$440k
NIAID NIH HHS R21 AI112717NIAID NIH HHS T32 AI007285NIAID NIH HHS T32 AI118689NIAID NIH HHS T32 AI118697NIGMS NIH HHS T32 GM063483NIH HHS HHSN266200700008CNIH HHS R21AI112717NIH HHS T32GM068411NIH HHS T32GM07356
6 · The paper itself

Abstract

Current influenza vaccines have modest efficacy. This is especially true for current live attenuated influenza vaccines (LAIV), which have been inferior to the inactivated versions in recent years. Therefore, a new generation of live vaccines may be needed. We previously showed that a mutation at PB1 residue 319 confers enhanced temperature sensitivity and attenuation in an LAIV constructed in the genetic background of the mouse-adapted Influenza A Virus (IAV) strain A/PR/8/34 (PR8). Here, we describe the origin/discovery of this unique mutation and demonstrate that, when combined with the PB2 N265S mutation of LAIV, it conveys an even greater level of temperature sensitivity and attenuation on PR8 than the complete set of attenuating mutations from LAIV. Furthermore, we show that the combined PB1 L319Q and PB2 N265S mutations confer temperature sensitivity on IAV polymerase activity in two different genetic backgrounds, PR8 and A/Cal/04/09. Collectively, these findings show that the PB2 LAIV mutation synergizes with a mutation in PB1 and may have potential utility for improving LAIVs.

Indexed as

MutationTemperatureA549 CellsAnimalsDNA-Directed DNA PolymeraseDogsFemaleHEK293 CellsHumansInfluenza A Virus, H1N1 SubtypeInfluenza VaccinesMadin Darby Canine Kidney CellsMiceMice, Inbred C57BLOrthomyxoviridae InfectionsRNA-Dependent RNA PolymeraseDNA-Directed DNA PolymeraseInfluenza Vaccinesinfluenza virus polymerase basic protein 1PB2 protein, Influenzavirus ARNA-Dependent RNA PolymeraseVaccines, AttenuatedViral ProteinsInfluenza A VirusLAIVpolymerasetemperature sensitivityvaccine

Identifiers

PMID33142846
PMCPMC7693792
OpenAlexW3097724940

What OpenQuestion holds

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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.