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

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)

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.

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Funder and Project Information

1

Genomics of human cytomegalovirus

Andrew Davison

MC_UU_12014/3

MVLS III - CENTRE FOR VIRUS RESEARCH

Viral Genomics and Bioinformatics

Andrew Davison

MC_UU_12014/12

III-MRC-GU Centre for Virus Research

Exploiting a human challenge model to understand the pathogenesis of cytomegalovirus

Andrew Davison

204870/Z/16/Z (17/0008)

III-MRC-GU Centre for Virus Research

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