Evidence map›Paper›PMID 40983723›Full record

ReviewNature protocols2026

Multidimensional analysis of host-virus interactions using the virus-encoded CRISPR-based direct readout system (VECOS).

Anna Lilja, Yaara Finkel, Einav Aharon, Aharon Nachshon, Michal Schwartz, Noam Stern-Ginossar

Abstract readReview
PubMed Publisher
In one paragraph

Review in Nature protocols, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.

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

0 citing papers in PubMed.

No citing paper in PubMed yet.

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

6 authors.

Anna Lilja *Department of Molecular Genetics, Weizmann Institute of Science, Rehovot, Israel.
Yaara Finkel *Department of Molecular Genetics, Weizmann Institute of Science, Rehovot, Israel.
Einav AharonDepartment of Molecular Genetics, Weizmann Institute of Science, Rehovot, Israel.
Aharon NachshonDepartment of Molecular Genetics, Weizmann Institute of Science, Rehovot, Israel.
Michal Schwartz *Department of Molecular Genetics, Weizmann Institute of Science, Rehovot, Israel. michalsc@weizmann.ac.il.ORCID 0000-0001-5442-0201
Noam Stern-Ginossar *Department of Molecular Genetics, Weizmann Institute of Science, Rehovot, Israel. noam.stern-ginossar@weizmann.ac.il.ORCID 0000-0003-3583-5932

Funding

EC | EU Framework Programme for Research and Innovation H2020 | H2020 Priority Excellent Science | H2020 European Research Council (H2020 Excellent Science - European Research Council) CoG-2019-864012
6 · The paper itself

Abstract

CRISPR-Cas9 technology has transformed the study of gene function, enabling the systematic investigation of host-virus interactions. However, most CRISPR-based screens in the context of viral infections rely on cell survival as a readout, which limits their sensitivity and biases results toward early infection stages. To address these challenges, we developed the virus-encoded CRISPR-based direct readout system (VECOS), a virus-centric approach in which human cytomegalovirus is engineered to express single-guide RNA (sgRNA) libraries directly from its genome. This system allows sgRNA abundance, embedded in the viral genome, to serve as a direct and quantitative readout of gene-perturbation effects on viral propagation. By tracking sgRNA levels at distinct stages of the viral infection cycle, VECOS enables a detailed, multidimensional analysis of virus-host interactions. Here we present a modular detailed Protocol for (1) constructing and reconstituting complex sgRNA libraries in double-stranded DNA viruses using bacterial artificial chromosomes, (2) performing multipassage screens to investigate perturbation effects on various stages of viral infection and (3) analyzing the multipassage and multistage sgRNA abundance measurements utilizing a comprehensive framework for data analysis. Successful implementation of this full Protocol takes 14-22 weeks and requires proficiency in molecular biology, as well as basic familiarity with Unix-based computing and programming in R for data processing. This Protocol offers researchers a robust tool for uncovering the molecular mechanisms that drive viral propagation and host-virus interactions.

Indexed as

CRISPR-Cas SystemsCytomegalovirusHost Microbial InteractionsHost-Pathogen InteractionsGenome, ViralHEK293 CellsHumansRNA, Guide, CRISPR-Cas SystemsRNA, Guide, CRISPR-Cas Systems

Identifiers

What OpenQuestion holds

Textmetadata
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.