Evidence map›Paper›PMID 37489888›Full record

ArticlemBio2023

Establishment of a CPER reverse genetics system for Powassan virus defines attenuating NS1 glycosylation sites and an infectious NS1-GFP11 reporter virus.

Jonas N Conde, Grace E Himmler, Megan C Mladinich, Yin Xiang Setoh, Alberto A Amarilla, William R Schutt, Nicholas Saladino, Elena E Gorbunova, Daniel J Salamango, Jorge Benach and 2 more

Open access · goldAbstract read
In one paragraph

Article in mBio, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 10 papers.

0numbers the graph read from it
0cells of the map it votes in
10citing papers in PubMed
2.9field-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

10 citing papers in PubMed, 10 citations in OpenAlex.

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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

12 authors at 3 institutions in 3 countries.

Jonas N Conde *Department of Microbiology and Immunology, Stony Brook University , Stony Brook, New York, USA.ORCID 0000-0001-5895-1114
Grace E Himmler *Department of Microbiology and Immunology, Stony Brook University , Stony Brook, New York, USA.
Megan C MladinichDepartment of Microbiology and Immunology, Stony Brook University , Stony Brook, New York, USA.
Yin Xiang SetohMicrobiology and Molecular Epidemiology Division, Environmental Health Institute, National Environmental Agency , Singapore, Singapore.
Alberto A AmarillaSchool of Chemistry and Molecular Biosciences, University of Queensland , St Lucia, Queensland, Australia.
William R SchuttDepartment of Microbiology and Immunology, Stony Brook University , Stony Brook, New York, USA.
Nicholas SaladinoDepartment of Microbiology and Immunology, Stony Brook University , Stony Brook, New York, USA.
Elena E GorbunovaDepartment of Microbiology and Immunology, Stony Brook University , Stony Brook, New York, USA.
Daniel J SalamangoDepartment of Microbiology and Immunology, Stony Brook University , Stony Brook, New York, USA.
Jorge BenachDepartment of Microbiology and Immunology, Stony Brook University , Stony Brook, New York, USA.
Hwan Keun KimDepartment of Microbiology and Immunology, Stony Brook University , Stony Brook, New York, USA.ORCID 0000-0003-2095-9705
Erich R MackowDepartment of Microbiology and Immunology, Stony Brook University , Stony Brook, New York, USA.ORCID 0000-0001-9156-1222
Stony Brook University · USThe University of Queensland · AUNational Environment Agency · SG

Funding

Antigen Specific Response to BorreliaR01AI027044 · NIAID · STATE UNIVERSITY NEW YORK STONY BROOK · PI BENACH, JORGE L. · 1989 to 2020
$3.7M
MOLECULAR AND CELL BIOLOGY OF INFECTIOUS DISEASEST32AI007539 · NIAID · STATE UNIVERSITY NEW YORK STONY BROOK · PI KONOPKA, JAMES B · 1998 to 2023
$3.6M
HHS | NIH | National Institute of Allergy and Infectious Diseases (NIAID) R01AI12901005HHS | NIH | National Institute of Allergy and Infectious Diseases (NIAID) R21AI13173902HHS | NIH | National Institute of Allergy and Infectious Diseases (NIAID) R21AI15237201HHS | NIH | National Institute of Allergy and Infectious Diseases (NIAID) RO1AI027044HHS | NIH | National Institute of Allergy and Infectious Diseases (NIAID) T32AI007539NIAID NIH HHS R01 AI027044NIAID NIH HHS T32 AI007539
6 · The paper itself

Abstract

Powassan virus (POWV) is an emerging tick-borne Flavivirus that causes lethal encephalitis and long-term neurologic damage. Currently, there are no POWV therapeutics, licensed vaccines, or reverse genetics systems for producing infectious POWVs from recombinant DNA. Using a circular polymerase extension reaction (CPER), we generated recombinant LI9 (recLI9) POWVs with attenuating NS1 protein mutations and a recLI9-split-eGFP reporter virus. NS1 proteins are highly conserved glycoproteins that regulate replication, spread, and neurovirulence. POWV NS1 contains three putative N-linked glycosylation sites that we modified individually in infectious recLI9 mutants (N85Q, N208Q, and N224Q). NS1 glycosylation site mutations reduced replication kinetics and were attenuated, with 1-2 log decreases in titer. Severely attenuated recLI9-N224Q exhibited a 2- to 3-day delay in focal cell-to-cell spread and reduced NS1 secretion but was lethal when intracranially inoculated into suckling mice. However, footpad inoculation of recLI9-N224Q resulted in the survival of 80% of mice and demonstrated that NS1-N224Q mutations reduce POWV neuroinvasion

Indexed as

Communicable DiseasesEncephalitis Viruses, Tick-BorneGlycosylationHumansReverse GeneticsSkinattenuationcell-to-cell spreadcircular polymerase extension reactionflavivirusNS1 glycosylation mutantsPowassan virusreverse geneticssplit-GFP

Identifiers

PMID37489888
PMCPMC10470542
OpenAlexW4385230273

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.