Human cytomegalovirus RNA2.7 is required for upregulating multiple cellular genes to promote cell motility and viral spread late in lytic infection

Lau, B. et al. (2021) Human cytomegalovirus RNA2.7 is required for upregulating multiple cellular genes to promote cell motility and viral spread late in lytic infection. Journal of Virology, 95(20), e00698-21. (doi: 10.1128/JVI.00698-21) (PMID:34346763) (PMCID:PMC8475523)

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Abstract

Long non-coding RNAs are frequently associated with broad modulation of gene expression and thus provide the cell with the ability to synchronize entire metabolic processes. We used transcriptomic approaches to investigate whether the most abundant human cytomegalovirus-encoded lncRNA, RNA2.7, has this characteristic. By comparing cells infected with wild-type virus (WT) with cells infected with RNA2.7 deletion mutants, RNA2.7 was implicated in regulating a large number of cellular genes late in lytic infection. Pathway analysis indicated that >100 of these genes are associated with promoting cell movement, and the ten most highly regulated of these were validated in further experiments. Morphological analysis and live cell tracking of WT- and RNA2.7 mutant-infected cells indicated that RNA2.7 is involved in promoting the movement and detachment of infected cells late in infection, and plaque assays using sparse cell monolayers indicated that RNA2.7 is also involved in promoting cell-to-cell spread of virus. Consistent with the observation that upregulated mRNAs are relatively A+U-rich, which is a trait associated with transcript instability, and that they are also enriched in motifs associated with mRNA instability, transcriptional inhibition experiments on WT- and RNA2.7 mutant-infected cells showed that four upregulated transcripts were longer-lived in the presence of RNA2.7. These findings demonstrate that RNA2.7 is required for promoting cell movement and viral spread late in infection and suggest that this may be due to general stabilization of A+U-rich transcripts.

Item Type:Articles
Status:Published
Refereed:Yes
Glasgow Author(s) Enlighten ID:Camiolo, Dr Salvatore and Suarez, Dr Nicolas and Lau, Dr Betty and Loney, Mr Colin and Gu, Dr Quan and Kerr, Mrs Karen and Davison, Professor Andrew
Creator Roles:
Lau, B.Conceptualization, Project administration, Supervision, Data curation, Formal analysis, Investigation, Validation, Visualization, Writing – original draft, Writing – review and editing
Davison, A. J.Conceptualization, Project administration, Supervision, Funding acquisition, Resources, Writing – original draft, Writing – review and editing
Camiolo, S.Data curation, Formal analysis, Software, Writing – review and editing
Gu, Q.Data curation, Formal analysis, Software
Kerr, K.Investigation, Validation
Suárez, N. M.Investigation
Loney, C.Investigation
Authors: Lau, B., Kerr, K., Camiolo, S., Nightingale, K., Gu, Q., Antrobus, R., Suárez, N. M., Loney, C., Stanton, R. J., Weekes, M. P., and Davison, A. J.
College/School:College of Medical Veterinary and Life Sciences > Institute of Infection Immunity and Inflammation
Journal Name:Journal of Virology
Publisher:American Society for Microbiology
ISSN:0022-538X
ISSN (Online):1098-5514
Published Online:04 August 2021
Copyright Holders:Copyright © 2021 Lau et al.
First Published:First published in Journal of Virology 95(20): e00698-21
Publisher Policy:Reproduced under a Creative Commons License

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Project CodeAward NoProject NamePrincipal InvestigatorFunder's NameFunder RefLead Dept
656321Genomics of human cytomegalovirusAndrew DavisonMedical Research Council (MRC)MC_UU_12014/3MVLS III - CENTRE FOR VIRUS RESEARCH
Viral Genomics and BioinformaticsAndrew DavisonMedical Research Council (MRC)MC_UU_12014/12III-MRC-GU Centre for Virus Research
174258Exploiting a human challenge model to understand the pathogenesis of cytomegalovirusAndrew DavisonWellcome Trust (WELLCOTR)204870/Z/16/Z (17/0008)III-MRC-GU Centre for Virus Research