A Viral Long Non-Coding RNA Protects against Cell Death during Human Cytomegalovirus Infection of CD14+ Monocytes.
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Publication Date
2022-01-26Journal Title
Viruses
ISSN
1999-4915
Publisher
MDPI AG
Volume
14
Issue
2
Language
eng
Type
Article
This Version
VoR
Metadata
Show full item recordCitation
Perera, M. R., Roche, K. L., Murphy, E. A., & Sinclair, J. H. (2022). A Viral Long Non-Coding RNA Protects against Cell Death during Human Cytomegalovirus Infection of CD14+ Monocytes.. Viruses, 14 (2) https://doi.org/10.3390/v14020246
Abstract
Long non-coding RNA β2.7 is the most highly transcribed viral gene during latent human cytomegalovirus (HCMV) infection. However, as yet, no function has ever been ascribed to β2.7 during HCMV latency. Here we show that β2.7 protects against apoptosis induced by high levels of reactive oxygen species (ROS) in infected monocytes, which routinely support latent HCMV infection. Monocytes infected with a wild-type (WT) virus, but not virus deleted for the β2.7 gene (Δβ2.7), are protected against mitochondrial stress and subsequent apoptosis. Protected monocytes display lower levels of ROS and additionally, stress-induced death in the absence of β2.7 can be reversed by an antioxidant which reduces ROS levels. Furthermore, we show that infection with WT but not Δβ2.7 virus results in strong upregulation of a cellular antioxidant enzyme, superoxide dismutase 2 (SOD2) in CD14+ monocytes. These observations identify a role for the β2.7 viral transcript, the most abundantly expressed viral RNA during latency but for which no latency-associated function has ever been ascribed, and demonstrate a novel way in which HCMV protects infected monocytes from pro-death signals to optimise latent carriage.
Keywords
Apoptosis, Reactive oxygen species, Oxidative stress, Human cytomegalovirus, Latency, Long Non-coding Rna, Monocytes, Cells, Cultured, Mitochondria, Humans, Cytomegalovirus, Reactive Oxygen Species, RNA, Viral, Antioxidants, Virus Latency, Oxidative Stress, Mutation, RNA, Long Noncoding, Lipopolysaccharide Receptors
Sponsorship
MRC
Funder references
Wellcome Trust (073979/Z/03/A)
Medical Research Council (MR/S00081X/1)
Identifiers
35215840, PMC8874509
External DOI: https://doi.org/10.3390/v14020246
This record's URL: https://www.repository.cam.ac.uk/handle/1810/335497
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