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Establishing lifelong infection and periodically shedding infectious progeny is a successful strategy employed by several persistent pathogens. In this issue of Cell Host & Microbe, Pan et al. (2014) demonstrate that a cell-type-specific host microRNA can restrict gene expression and pathogenicity of herpes simplex virus 1, thereby promoting long-term infection., (Copyright © 2014 Elsevier Inc. All rights reserved.)

RNA interference (RNAi) is an established antiviral defense mechanism in plants and invertebrates. Whether RNAi serves a similar function in mammalian cells remains unresolved. We find that in some cell types, mammalian RNAi activity is reduced shortly after viral infection via poly-ADP-ribosylation of the RNA-induced silencing complex (RISC), a core component of RNAi. Well-established antiviral signaling pathways, including RIG-I/MAVS and RNaseL, contribute to inhibition of RISC. In the absence of virus infection, microRNAs repress interferon-stimulated genes (ISGs) associated with cell death and proliferation, thus maintaining homeostasis. Upon detection of intracellular pathogen-associated molecular patterns, RISC activity decreases, contributing to increased expression of ISGs. Our results suggest that, unlike in lower eukaryotes, mammalian RISC is not antiviral in some contexts, but rather RISC has been co-opted to negatively regulate toxic host antiviral effectors via microRNAs., (Copyright © 2013 Elsevier Inc. All rights reserved.)

Kaposi's sarcoma-associated herpes virus (KSHV), the causative agent of several neoplasms, has recently been shown to encode 12 microRNAs. mir-155 is a host-encoded microRNA associated with lymphomagenesis. Two new papers provide strong evidence that a KSHV-encoded microRNA and mir-155 share a common set of mRNA targets and binding sites, implying a possible link between viral- and non-viral-mediated tumorigenesis.

MicroRNAs (miRNAs) play a pivotal role in the regulation of genes involved in diverse processes such as development, differentiation, and cellular growth control. Recently, many viral-encoded miRNAs have been discovered, for the most part in viruses transcribed from double-stranded DNA genomes. As with their cellular counterparts, the functions of most viral-derived miRNAs are unknown; however, functions have been documented or proposed for viral miRNAs from three different viral families-herpesviruses, polyomaviruses, and retroviruses. Several virus-encoded miRNAs have unique aspects to their biogenesis, such as the polymerase that transcribes them or their location within the precursor transcript. Additionally, viral interactions with cellular miRNAs have also been identified, and these have substantially expanded our appreciation of miRNA functions.