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MicroRNAs (miRNAs), which can be expressed in a cell-type and tissue-specific manner, can influence the activities of genes that control cell growth and differentiation. Viruses often have clear tissue tropisms, raising the possibility that cellular miRNAs might modulate their pathogenesis. In this Review, we discuss recent findings that some vertebrate viruses either encode miRNAs or subvert cellular miRNAs, and that these miRNAs participate in both the infectious and the latent phase of the viral life cycle.

Brain and leptomeningeal metastases are common in breast cancer patients and our current treatments are ineffective. Reovirus type 3 is a replication competent, naturally occurring virus that usurps the activated Ras-signaling pathway (or an element thereof) of tumor cells and lyses them but leaves normal cells relatively unaffected. In this study we evaluated reovirus as an experimental therapeutic in models of central nervous system (CNS) metastasis from breast cancer. We found all breast cancer cell lines tested were susceptible to reovirus, with > 50% of these cells lysed within 72 h of infection. In vivo neurotoxicity studies showed only mild local inflammation at the injection site and mild communicating hydrocephalus with neither diffuse encephalitis nor behavioral abnormalities at the therapeutically effective dose of reovirus (intracranial) (ie 10(7) plaque-forming units) or one dose level higher. In vivo, a single intratumoral administration of reovirus significantly reduced the size of tumors established from two human breast cancer cell lines and significantly prolonged survival. Intrathecal administration of reovirus also remarkably prolonged survival in an immunocompetent racine model of leptomeningeal metastases. These data suggest that the evaluation of reovirus as an experimental therapeutic for CNS metastases from breast cancer is warranted.

Hepatitis C virus (HCV) is an important human liver pathogen that has infected over 170 million people worldwide, often leading to liver cirrhosis and hepatocellular carcinoma 1. While the efficacies of novel inhibitors of the viral polymerase and protease enzymes are being explored in numerous clinical trials, current therapies against HCV infections are limited to a combined administration of pegylated interferon-α and ribavirin. However, this combination therapy has considerable side effects, which include influenza-like symptoms, depression and anemia 2. Moreover, even after 48 weeks of therapy, sustained virologic response rates are observed in only half of the patients infected with the prevalent genotype 1 HCV 2. Thus, there is a need for exploring novel therapeutic approaches that target both viral and host factors that are essential for viral growth.