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

Long non-coding RNA beta 2.7 is the most highly transcribed viral gene during latent human cytomegalovirus (HCMV) infection. However, as yet, no function has ever been ascribed to beta 2.7 during HCMV latency. Here we show that beta 2.7 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 beta 2.7 gene (Delta beta 2.7), are protected against mitochondrial stress and subsequent apoptosis. Protected monocytes display lower levels of ROS and additionally, stress-induced death in the absence of beta 2.7 can be reversed by an antioxidant which reduces ROS levels. Furthermore, we show that infection with WT but not Delta beta 2.7 virus results in strong upregulation of a cellular antioxidant enzyme, superoxide dismutase 2 (SOD2) in CD14+ monocytes. These observations identify a role for the beta 2.7 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.