Functional single-cell genomics of human cytomegalovirus infection

Understanding how viral and host factors interact and how perturbations impact infection is the basis for designing antiviral interventions. Here we define the functional contribution of each viral and host factor involved in human cytomegalovirus infection in primary human fibroblasts through poole...

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Bibliographic Details
Published in:Nature biotechnology 2022-03, Vol.40 (3), p.391-401
Main Authors: Hein, Marco Y., Weissman, Jonathan S.
Format: Article
Language:English
Subjects:
631/114/2163
631/1647
631/208/191
631/326/596/2097
631/61/191
Agriculture
Bioinformatics
Biomedical and Life Sciences
Biomedical Engineering/Biotechnology
Biomedicine
Biotechnology
Clustered Regularly Interspaced Short Palindromic Repeats - genetics
CRISPR
Cytomegalovirus
Cytomegalovirus Infections - genetics
Fibroblasts
Genomics
Host-pathogen interactions
Host-Pathogen Interactions - genetics
Humans
Infections
Life Sciences
Nuclease
Perturbation
Transcription
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Summary:Understanding how viral and host factors interact and how perturbations impact infection is the basis for designing antiviral interventions. Here we define the functional contribution of each viral and host factor involved in human cytomegalovirus infection in primary human fibroblasts through pooled CRISPR interference and nuclease screening. To determine how genetic perturbation of critical host and viral factors alters the timing, course and progression of infection, we applied Perturb-seq to record the transcriptomes of tens of thousands of CRISPR-modified single cells and found that, normally, most cells follow a stereotypical transcriptional trajectory. Perturbing critical host factors does not change the stereotypical transcriptional trajectory per se but can stall, delay or accelerate progression along the trajectory, allowing one to pinpoint the stage of infection at which host factors act. Conversely, perturbation of viral factors can create distinct, abortive trajectories. Our results reveal the roles of host and viral factors and provide a roadmap for the dissection of host–pathogen interactions. Pooled and single-cell CRISPR screens provide a detailed map of human cytomegalovirus infection.
ISSN:1087-0156
1546-1696
DOI:10.1038/s41587-021-01059-3