Evidence map›Paper›PMID 37605152›Full record

ArticleRetrovirology2023

Analysis of PERV-C superinfection resistance using HA-tagged viruses.

Merle Flecks, Nicole Fischer, Jacomina Krijnse Locker, Ralf R Tönjes, Antonia W Godehardt

Erratum issuedOpen access · goldAbstract read
In one paragraph

Article in Retrovirology, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. An erratum has been issued. Cited by 1 paper.

0numbers the graph read from it
0cells of the map it votes in
1citing papers in PubMed
0.3field-weighted citation impact, top 38% 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

1 citing paper in PubMed, 1 citations in OpenAlex.

  1. Article
4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

5 authors at 1 institution in 1 country.

Merle FlecksDivision of Haematology, Cell and Gene Therapy, Paul-Ehrlich-Institut, Langen, Germany.
Nicole FischerDivision of Haematology, Cell and Gene Therapy, Paul-Ehrlich-Institut, Langen, Germany.
Jacomina Krijnse LockerLoewe-DRUID Research Group, Electron Microscopy of Pathogens, Paul-Ehrlich-Institut, Langen, Germany.
Ralf R TönjesDivision of Haematology, Cell and Gene Therapy, Paul-Ehrlich-Institut, Langen, Germany.
Antonia W GodehardtDivision of Haematology, Cell and Gene Therapy, Paul-Ehrlich-Institut, Langen, Germany. Antonia.Godehardt@pei.de.
Paul Ehrlich Institut · DE

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

backgroundUsing pigs as organ donors has advanced xenotransplantation to the point that it is almost ready for clinical use. However, there is still a zoonotic risk associated with xenotransplantation, and the potential transmission of porcine endogenous retroviruses needs to be surveyed. Despite significant attempts to eliminate this risk, by the selection of PERV-C free pigs with low expression of PERV-A, -B, and by the genome-wide inactivation of PERV using CRISPR/Cas9, the impact of superinfection resistance (SIR) was not investigated. SIR is a viral trait that prevents reinfection (superinfection). For PERV, the underlying mechanism is unclear, whether and how cells, that harbor functional PERV, are protected. Using PERV-C(5683) as a reference virus, we investigated SIR in a newly developed in vitro model to pursue the mechanism and confirm its protective effect.

resultsWe developed three PERV-C constructs on the basis of PERV-C(5683), each of which carries a hemagglutinin tag (HA-tag) at a different position of the envelope gene (SP-HA, HA-VRA, and RPep-HA), to distinguish between primary infection and superinfection. The newly generated PERV-C(5683)-HA viruses were characterized while quantifying the viral RNA, reverse transcriptase activity, protein expression analysis, and infection studies. It was demonstrated that SP-HA and RPep-HA were comparable to PERV-C(5683), whereas HA-VRA was not replication competent. SP-HA and RPep-HA were chosen to challenge PERV-C(5683)-positive ST-IOWA cells demonstrating that PERV-C-HA viruses are not able to superinfect those cells. They do not integrate into the genome and are not expressed.

conclusionsThe mechanism of SIR applies to PERV-C. The production of PERV-C particles serves as a defense mechanism from superinfection with exogenous PERV-C. It was demonstrated by newly generated PERV-C(5683)-HA clones that might be used as a cutting-edge tool. The HA-tagging of PERV-C is novel, providing a blueprint for the tagging of other human tropic PERV viruses. The tagged viruses are suitable for additional in vitro and in vivo infection studies and will contribute, to basic research on viral invasion and pathogenesis. It will maintain the virus safety of XTx.

Indexed as

GammaretrovirusSuperinfectionAnimalsGenes, envHumansPhenotypeRNA, ViralSwineRNA, ViralEnv proteinHA-tagPorcine endogenous retrovirusSuperinfection resistanceVirological safetyXenotransplantation

Identifiers

PMID37605152
PMCPMC10440901
OpenAlexW4386031078

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.