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A Viral Long Non-Coding RNA Protects against Cell Death during Human Cytomegalovirus Infection of CD14+ Monocytes.

Published version
Peer-reviewed

Type

Article

Change log

Authors

Roche, Kathryn L 
Murphy, Eain A 
Sinclair, John H 

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.

Description

Keywords

apoptosis, human cytomegalovirus, latency, long non-coding RNA, oxidative stress, reactive oxygen species, Antioxidants, Apoptosis, Cells, Cultured, Cytomegalovirus, Humans, Lipopolysaccharide Receptors, Mitochondria, Monocytes, Mutation, Oxidative Stress, RNA, Long Noncoding, RNA, Viral, Reactive Oxygen Species, Virus Latency

Journal Title

Viruses

Conference Name

Journal ISSN

1999-4915
1999-4915

Volume Title

14

Publisher

MDPI AG
Sponsorship
Wellcome Trust (073979/Z/03/A)
Medical Research Council (MR/S00081X/1)
MRC