In a recent study entitled “Pan-viral-microRNA screening identifies interferon inhibition as a common function of diverse viruses” researchers showed that Herpes viruses such as Epstein-Barr virus, a tumor causing pathogen, have microRNAs that impair the antiviral cytokine interferon response of the immune system. These findings have unlocked a new understanding of why certain tumors originating from herpes viruses infection are resistant to interferon therapy. The study was published in the journal Proceedings of the National Academy of Sciences (PNAS).
Epstein-Barr virus is associated with multiple cancers, including gastric cancers, lymphomas and nasopharyngeal cancers. Viruses carry a class of regulatory RNAs – microRNAs (miRNAs) — that are capable of regulating multiple processes. In this sense, by secreting these RNA molecules viruses can hijack cellular functions, usually enhancing their infection. However, the majority of viral miRNAs functions, as well as its cellular targets, remain largely unknown.
A team of researchers at the University of Texas, Austin and the University of California, San Francisco screened a library of more than 70 human viral miRNAs, under the premise that the functions of miRNAs molecules are shared between different viruses. Accordingly, the researchers found three miRNAs species among herpes viruses that target the interferon signaling pathway, a key response of the human’s innate immune system, significantly inhibiting it. Specifically, the authors identified a central component of the interferon pathway, the cyclic AMP-responsive element-binding protein (CBP), as target of these miRNAs. As a result, the two specific miRNAs from Epstein–Barr virus and Rhesus lymphocryptovirus that impair interferon signaling were identified. Therefore, these findings show that several herpes viruses target the interferon response via the same regulatory mechanism. The team performed further studies on tumor cells positive for Epstein–Barr virus by blocking the identified miRNA they were capable of overcoming the initial interferon-resistance, rendering tumor cells susceptible to interferon therapy. The clinical implications are obvious, and while still at the embryonic stage, future research may open new therapeutic avenues for cancer-associated viruses.