Evidence map›Paper›PMID 33213424›Full record

ArticleBMC veterinary research2020

Multi-targeted gene silencing strategies inhibit replication of Canine morbillivirus.

Otávio Valério de Carvalho, Marcus Rebouças Santos, Juliana Lopes Rangel Fietto, Mauro Pires Moraes, Márcia Rogéria de Almeida, Gustavo Costa Bressan, Lindomar José Pena, Abelardo Silva-Júnior

Open access · goldAbstract read
In one paragraph

Article in BMC veterinary research, 2020. 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
0.4field-weighted citation impact, top 31% 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, 3 citations in OpenAlex.

  1. Article
  2. 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 2 institutions in 1 country.

Otávio Valério de CarvalhoLaboratory of Immunobiological and Animal Virology, Department of Veterinary Medicine, Federal University of Viçosa, Av. Peter Henry Rolfs, s/n, Viçosa, MG, 36570-000, Brazil.
Marcus Rebouças SantosLaboratory of Immunobiological and Animal Virology, Department of Veterinary Medicine, Federal University of Viçosa, Av. Peter Henry Rolfs, s/n, Viçosa, MG, 36570-000, Brazil.
Juliana Lopes Rangel FiettoDepartment of Biochemistry and Molecular Biology, Federal University of Viçosa, Av. Peter Henry Rolfs, s/n, Viçosa, MG, 36570-000, Brazil.
Mauro Pires MoraesLaboratory of Immunobiological and Animal Virology, Department of Veterinary Medicine, Federal University of Viçosa, Av. Peter Henry Rolfs, s/n, Viçosa, MG, 36570-000, Brazil.
Márcia Rogéria de AlmeidaDepartment of Biochemistry and Molecular Biology, Federal University of Viçosa, Av. Peter Henry Rolfs, s/n, Viçosa, MG, 36570-000, Brazil.
Gustavo Costa BressanDepartment of Biochemistry and Molecular Biology, Federal University of Viçosa, Av. Peter Henry Rolfs, s/n, Viçosa, MG, 36570-000, Brazil.
Lindomar José PenaDepartment of Virology and Experimental Therapy, Oswaldo Cruz Foundation (FIOCRUZ), Aggeu Magalhães Research Center, Av. Moraes Rego, s/n, Campus UFPE, Cidade Universitária, Recife, PE, 50670-420, Brazil. lindomar.pena@cpqam.fiocruz.br.
Abelardo Silva-JúniorDepartment of Virology and Experimental Therapy, Oswaldo Cruz Foundation (FIOCRUZ), Aggeu Magalhães Research Center, Av. Moraes Rego, s/n, Campus UFPE, Cidade Universitária, Recife, PE, 50670-420, Brazil. abelardo.junior@ufv.br.
Universidade Federal de Viçosa · BRFundação Oswaldo Cruz · BR

Funding

Conselho Nacional de Desenvolvimento Científico e Tecnológico 307701/2019-0Coordenação de Aperfeiçoamento de Pessoal de Nível Superior 23038.004809/2018-16
6 · The paper itself

Abstract

backgroundCanine morbilivirus (canine distemper virus, CDV) is a highly contagious pathogen associated with high morbidity and mortality in susceptible carnivores. Although there are CDV vaccines available, the disease poses a huge threat to dogs and wildlife hosts due to vaccine failures and lack of effective treatment. Thus, the development of therapeutics is an urgent need to achieve rapid outbreak control and reduce mortality in target species. Gene silencing by RNA interference has emerged as a promising therapeutic approach against different human and animal viruses. In this study, plasmid-based short hairpin RNAs (shRNAs) against three different regions in either CDV nucleoprotein (N), or large polymerase (L) genes and recombinant adenovirus-expressing N-specific multi-shRNAs were generated. Viral cytopathic effect, virus titration, plaque-forming unit reduction, and real-time quantitative RT-PCR analysis were used to check the efficiency of constructs against CDV.

resultsIn CDV-infected VerodogSLAM cells, shRNA-expressing plasmids targeting the N gene markedly inhibited the CDV replication in a dose-dependent manner, with viral genomes and titers being decreased by over 99%. Transfection of plasmid-based shRNAs against the L gene displayed weaker inhibition of viral RNA level and virus yield as compared to CDV N shRNAs. A combination of shRNAs targeting three sites in the N gene considerably reduced CDV RNA and viral titers, but their effect was not synergistic. Recombinant adenovirus-expressing multiple shRNAs against CDV N gene achieved a highly efficient knockdown of CDV N mRNAs and successful inhibition of CDV replication.

conclusionsWe found that this strategy had strong silencing effects on CDV replication in vitro. Our findings indicate that the delivery of shRNAs using plasmid or adenovirus vectors potently inhibits CDV replication and provides a basis for the development of therapeutic strategies for clinical trials.

Indexed as

RNA InterferenceRNA, Small InterferingAdenoviridaeAnimalsCell LineDistemperDistemper Virus, CanineDogsGene TargetingGenetic TherapyHEK293 CellsHumansPlasmidsVirus ReplicationRNA, Small InterferingAdenoviral vectorGene therapyMorbillivirusRNA interference

Identifiers

PMID33213424
PMCPMC7676405
OpenAlexW3098746978

What OpenQuestion holds

Textmetadata
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.