Human cytomegalovirus latent infection alters the expression of cellular and viral microRNA

The immunology of human cytomegalovirus latency: could latent infection be cleared by novel immunotherapeutic strategies?

“…miR-UL112.1 targets MICB a cellular stress (infection)-induced ligand, which usually functions by binding the homodimeric NK cell activating receptor NKG2D; 54 miR-US4.1 downregulates ERAP-1 which is an aminopeptidase which trims peptides for presentation by MHC Class I and reduced ERAP-1 expression decreasing HCMV-specific CD8 1 CTL recognition of HCMVinfected cells; 55 miR-UL148D targets the chemokine CCL5 (RANTES) which is a T-cell chemoattractant. 56 Interestingly, miR-UL112.1 and miR-US4.1 have been detected in quiescently infected THP1 cells 57,58 and we have also detected all three viral mRNAs in experimentally latent CD34 1 cells and CD14 1 monocytes (IHW Gdansk, Poland, 2012 and CMV meeting San Francisco, USA, 2013; Lau et al, unpubl. data).…”

“…62 Interestingly, quiescent infection of THP1 cells has also been shown to alter cellular miRNA expression. 58 Thus, it is clear that latent infection is far from a passive interaction between the virus and the cell; latent infection results directly in numerous changes in the cell phenotype which likely optimize the cell for latent carriage and reactivation. It is also likely that expression of latency-associated viral miRNAs and modulation of the cellular miRNAome plays a major part in orchestrating such changes in cellular gene expression and this strategy circumvents expression of viral functions which would be normally be surveilled by host immune responses.…”

In vivo expression of human cytomegalovirus (HCMV) microRNAs during latency

“…However, over the course of infection, a subset of the microRNAs: miR-US25-2-5p, miR-US29-5p, miR-US25-1-5p and miR-US5-2-3p disappeared gradually. Recently, Fu et al (Fu et al, 2014) have reported that miR-US25-1-5p and miR-US25-2-5p were expressed in latently infected THP-1 cells. However, in our hands; these two microRNAs were only transiently expressed at the early stage of latency (Fig.…”

Human cytomegalovirus miR-UL112-1 promotes the down-regulation of viral immediate early-gene expression during latency to prevent T-cell recognition of latently infected cells

“…Instead, viral gene expression during latency is probably reduced to those that play an important role in establishment and maintenance of the latent life cycle, and functions for proteins encoded by many of these latencyassociated transcripts are now beginning to be elucidated (Keyes et al, 2012b;Poole et al, 2014Poole et al, , 2015Tarrant-Elorza et al, 2014;Weekes et al, 2013). In addition to these, it is also becoming clear that known viral non-coding RNAs are also expressed during latency (Rossetto et al, 2013) and these include viral microRNAs (miRNAs) (Fu et al, 2014;Meshesha et al, 2016;Shen et al, 2014). Although the functional targets of a number of viral miRNAs expressed during lytic infection have been described (for reviews see: Dhuruvasan et al, 2011;Goldberger & Mandelboim, 2014;Hook et al, 2014a), little is known about the role of HCMV-encoded miRNAs during latency.…”