Viral miRNAs: tools for immune evasion

Abstract

MicroRNAs (miRNAs) are noncoding RNA molecules approximately 22 nucleotides in length that post-transcriptionally regulate gene expression by complementary binding to target mRNAs. MiRNAs have been identified in a diverse range of both metazoan and plant species. Functionally, miRNAs modulate multiple cellular processes including development, hematopoiesis, immunity, and oncogenesis. More recently, DNA viruses were found to encode and express miRNAs during host infection. Although the functions of most viral miRNAs are not well understood, early analysis of target genes pointed to immune modulation suggesting that viral miRNAs are a component of the immune evasion repertoire, which facilitates viral persistence. In addition to directly targeting immune functions, viral encoded miRNAs contribute to immune evasion by targeting proapoptotic genes, and in the case of herpesviruses, by controlling viral latency. Here we summarize the recently discovered targets of viral miRNAs and discuss the complex nature of this novel emerging regulatory mechanism.

Figure 1. DNA virus miRNAs regulate the host immune response

Host cells are infected by DNA viruses that replicate in the nucleus. After nuclear processing, viral miRNAs are exported into the cytoplasm where they are incorporated into RISC. Viral miRNAs then target multiple arms of the immune system by regulating expression of both host and viral mRNAs involved in cell-mediated immunity, apoptosis, cell cycle regulation, and viral latency.