Connivance, Complicity, or Collusion? The Role of Noncoding RNAs in Promoting Gammaherpesvirus Tumorigenesis

EBV and KSHV are etiologic agents of multiple types of lymphomas and carcinomas. The frequency of EBV⁺ or KSHV⁺ malignancies arising in immunocompromised individuals reflects the intricate evolutionary balance established between these viruses and their immunocompetent hosts. However, the specific mechanisms by which these pathogens drive tumorigenesis remain poorly understood. In recent years an enormous array of cellular and viral noncoding RNAs (ncRNAs) have been discovered, and host ncRNAs have been revealed as contributory factors to every single cancer hallmark cellular process. As new evidence emerges that gammaherpesvirus ncRNAs also alter host processes and viral factors dysregulate host ncRNA expression, and as novel viral ncRNAs continue to be discovered, we examine the contribution of small, non-miRNA ncRNAs and long ncRNAs to gammaherpesvirus tumorigenesis.