Applications of Deep Mutational Scanning in Virology

Overview

Journal Viruses

Publisher MDPI

Specialty Microbiology

Date 2021 Jun 2

PMID 34071591

Citations 5

Authors

Thomas D Burton

Nicholas S Eyre

Affiliations

Soon will be listed here.

Abstract

Several recently developed high-throughput techniques have changed the field of molecular virology. For example, proteomics studies reveal complete interactomes of a viral protein, genome-wide CRISPR knockout and activation screens probe the importance of every single human gene in aiding or fighting a virus, and ChIP-seq experiments reveal genome-wide epigenetic changes in response to infection. Deep mutational scanning is a relatively novel form of protein science which allows the in-depth functional analysis of every nucleotide within a viral gene or genome, revealing regions of importance, flexibility, and mutational potential. In this review, we discuss the application of this technique to RNA viruses including members of the Flaviviridae family, Influenza A Virus and Severe Acute Respiratory Syndrome Coronavirus 2. We also briefly discuss the reverse genetics systems which allow for analysis of viral replication cycles, next-generation sequencing technologies and the bioinformatics tools that facilitate this research.

Citing Articles

Crystallographic fragment screening and deep mutational scanning of Zika virus NS2B-NS3 protease enable development of resistance-resilient inhibitors.

von Delft F, Ni X, Richardson R, Godoy A, Ferla M, Kikawa C Res Sq. 2025; .

PMID: 39989958 PMC: 11844641. DOI: 10.21203/rs.3.rs-5876218/v1.

Deep mutationally scanned (DMS) CHIKV E3/E2 virus library maps viral amino acid preferences and predicts viral escape mutants of neutralizing CHIKV antibodies.

Stumpf M, Brunetti T, Davenport B, McCarthy M, Morrison T bioRxiv. 2024; .

PMID: 39677653 PMC: 11643203. DOI: 10.1101/2024.12.04.626854.

Integrating Computational Design and Experimental Approaches for Next-Generation Biologics.

Son A, Park J, Kim W, Lee W, Yoon Y, Ji J Biomolecules. 2024; 14(9).

PMID: 39334841 PMC: 11430650. DOI: 10.3390/biom14091073.

Mapping mutational fitness effects across the coxsackievirus B3 proteome reveals distinct profiles of mutation tolerability.

Alvarez-Rodriguez B, Velandia-Alvarez S, Toft C, Geller R PLoS Biol. 2024; 22(7):e3002709.

PMID: 39012844 PMC: 11251597. DOI: 10.1371/journal.pbio.3002709.

Crystallographic fragment screening and deep mutational scanning of Zika virus NS2B-NS3 protease enable development of resistance-resilient inhibitors.

Ni X, Richardson R, Godoy A, de Godoy A, Ferla M, Kikawa C bioRxiv. 2024; .

PMID: 38746305 PMC: 11092485. DOI: 10.1101/2024.04.29.591502.

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