MicroRNAs and CMV A number of viral microRNAs have been found in CMV. The function of the majority of these is largely unknown. Recently, the function of a specific microRNA (miR-UL-112-1) encoded by CMV was partially elucidated. Stern-Ginossar et al. used a new bioinformatics tool to identify the major histocompatibility complex (MHC) class I-related chain B (MICB) mRNA as a target of a miRNA encoded by CMV. MICB is a cellular ligand for the activating receptor NKG2D, which is expressed on some natural killer cells, γ/δ T cells, and CD8+ T cells. During cellular stress, such as that caused by viral infection, MICB is induced, thus activating natural killer and T cells that can lead to the killing of infected cells. Therefore blocking this process would probably benefit the virus. Stern-Ginossar et al. showed that cells infected with CMV that have been engineered to lack the miR-UL112-1 were more susceptible to being killed in an NKG2D-dependent manner by natural killer cells. The CMV-encoded protein UL16, also provides protection against the detection of infected cells by natural killer cells, by sequestering MICB in the intracellular milieu and preventing it from reaching the cell surface. Why the virus has two different mechanisms to achieve the same goal is not clear, particularly since the closely related NKG2D-ligand MICA is induced during viral infection. Members of my laboratory and I have recently described2 another function of the same miRNA. Successful, persistent infection depends on the maintenance of cell viability despite the production of toxic viral proteins. One way in which CMV can restrict the production of viral proteins is by restricting viral replication. We observed that miR-UL112-1 down-regulates the expression of CMV genes involved in its own replication process, in part by targeting a viral mRNA (encoding a protein called immediate early 72) that regulates the transcription of viral genes required for acute replication.