Evidence map›Paper›PMID 39207135›Full record

ArticleJournal of virology2024

A nanobody interaction with SARS-COV-2 Spike allows the versatile targeting of lentivirus vectors.

Ayna Alfadhli, Timothy A Bates, Robin Lid Barklis, CeAnn Romanaggi, Fikadu G Tafesse, Eric Barklis

Abstract read
In one paragraph

Article in Journal of virology, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 1 paper.

0numbers the graph read from it
0cells of the map it votes in
1citing 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

1 citing paper in PubMed.

  1. Article
4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

6 authors.

Ayna AlfadhliDepartment of Molecular Microbiology and Immunology, Oregon Health and Sciences University, Portland, Oregon, USA.
Timothy A BatesDepartment of Molecular Microbiology and Immunology, Oregon Health and Sciences University, Portland, Oregon, USA.
Robin Lid BarklisDepartment of Molecular Microbiology and Immunology, Oregon Health and Sciences University, Portland, Oregon, USA.
CeAnn RomanaggiDepartment of Molecular Microbiology and Immunology, Oregon Health and Sciences University, Portland, Oregon, USA.
Fikadu G TafesseDepartment of Molecular Microbiology and Immunology, Oregon Health and Sciences University, Portland, Oregon, USA.ORCID 0000-0002-8575-4164
Eric BarklisDepartment of Molecular Microbiology and Immunology, Oregon Health and Sciences University, Portland, Oregon, USA.ORCID 0000-0003-4944-6671

Funding

HIV-1 Gag Precursor Protein InteractionsR01AI152579 · NIAID · OREGON HEALTH & SCIENCE UNIVERSITY · PI BARKLIS, ERIC W · 2020 to 2024
$2.5M
Determining the role of sphingolipids in Mycobacterium tuberculosis infectionR01AI141549 · NIAID · OREGON HEALTH & SCIENCE UNIVERSITY · PI TAFESSE, FIKADU G. · 2020 to 2025
$2.4M
NIAID NIH HHS R01 AI141549NIAID NIH HHS R01 AI152579
6 · The paper itself

Abstract

While investigating methods to target gene delivery vectors to specific cell types, we examined the potential of using a nanobody against the SARS-CoV-2 Spike protein receptor-binding domain to direct lentivirus infection of Spike-expressing cells. Using four different approaches, we found that lentiviruses with surface-exposed nanobody domains selectively infect Spike-expressing cells. Targeting is dependent on the fusion function of the Spike protein, and conforms to a model in which nanobody binding to the Spike protein triggers the Spike fusion machinery. The nanobody-Spike interaction also is capable of directing cell-cell fusion and the selective infection of nanobody-expressing cells by Spike-pseudotyped lentivirus vectors. Significantly, cells infected with SARS-CoV-2 are efficiently and selectively infected by lentivirus vectors pseudotyped with a chimeric nanobody protein. Our results suggest that cells infected by any virus that forms syncytia may be targeted for gene delivery by using an appropriate nanobody or virus receptor mimic. Vectors modified in this fashion may prove useful in the delivery of immunomodulators to infected foci to mitigate the effects of viral infections.IMPORTANCEWe have discovered that lentiviruses decorated on their surfaces with a nanobody against the SARS-CoV-2 Spike protein selectively infect Spike-expressing cells. Infection is dependent on the specificity of the nanobody and the fusion function of the Spike protein and conforms to a reverse fusion model, in which nanobody binding to Spike triggers the Spike fusion machinery. The nanobody-Spike interaction also can drive cell-cell fusion and infection of nanobody-expressing cells with viruses carrying the Spike protein. Importantly, cells infected with SARS-CoV-2 are selectively infected with nanobody-decorated lentiviruses. These results suggest that cells infected by any virus that expresses an active receptor-binding fusion protein may be targeted by vectors for delivery of cargoes to mitigate infections.

Indexed as

Genetic VectorsLentivirusSARS-CoV-2Single-Domain AntibodiesSpike Glycoprotein, CoronavirusCell FusionCOVID-19Gene Transfer TechniquesHEK293 CellsHumansProtein BindingVirus InternalizationSingle-Domain AntibodiesSpike Glycoprotein, Coronavirusspike protein, SARS-CoV-2envelopelentivirusSARS-CoV-2

Identifiers

PMID39207135
PMCPMC11406891

What OpenQuestion holds

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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.