The use of microRNA by human viruses: lessons from NK cells and HCMV infection

Abstract

Depending on ethnicity and on social conditions, between 40 and 90 % of the population is infected with human cytomegalovirus (HCMV). In immunocompetent patients, the virus may cause an acute disease and then revert to a state of latency, which enables its coexistence with the human host. However, in cases of immunosuppression or in neonatal infections, HCMV can cause serious long-lasting illnesses. HCMV has developed multiple mechanisms in order to escape its elimination by the immune system, specifically by two killer cell types of the adaptive and the innate immune systems; cytotoxic T lymphocytes (CTL) and natural killer (NK) cells, respectively. Another fascinating aspect of HCMV is that like other highly developed herpesviruses, it expresses its own unique set of microRNAs. Here, we initially describe how the activity of NK cells is regulated under normal conditions and during infection. Then, we discuss what is currently known about HCMV microRNA-mediated interactions, with special emphasis on immune modulation and NK cell evasion. We further illustrate the significant modulation of cellular microRNAs during HCMV infection. Although, the full target spectrum of HCMV microRNAs is far from being completely elucidated, it can already be concluded that HCMV uses its "multitasking" microRNAs to globally affect its own life cycle, as well as important cellular and immune-related pathways.

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

“…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.…”

DNA damage response (DDR) and senescence: shuttled inflamma-miRNAs on the stage of inflamm-aging

“…A core temporal response to infection, shared across bacteria, has recently been described; it comprises a set of miRNAs, including miR-155, that may play an essential role in the regulation of basic cellular responses to stress [ 126 ]. Notably, DNA viruses encode viral miRNA, which can interfere with many cellular activities [ 127 , 128 , 129 ]. A relevant example is miR-155-like encoded by Kaposi sarcoma (KS) virus [ 95 ].…”

NK cell interplay with cytomegaloviruses

“…(b) HCMV strategies for interference with NKG2D include intracellular retention of the MICA/ULBP3 by the viral protein UL142 and of ULBP1/ULBP2/ULBP6 by the viral protein UL16 [46]. In addition to intracellular sequestration, the surface expression of MICB is further disrupted by miR-UL112, which binds MICB mRNA and inhibits translation, while MICA is targeted to lysosomal degradation by the concerted actions of US18 and US20 [46,84,85]. MICA*008 is unaffected by US18, US20 and UL142 and is specifically targeted by US9.…”