Noncanonical viral miRNA functions.

<p>(A) The use of host miRNA biogenesis machinery to modulate mRNA in <i>cis</i> has been reported in two different herpesviruses. On the left, the KSHV gene Kaposin B (KapB) functions as both an mRNA encoding a protein and a pri-miRNA for two KSHV-encoded miRNAs. Each KapB transcript may function as either an mRNA or pri-miRNA, but not both since pre-miRNA biogenesis occurs in the nucleus and destroys the mRNA. The levels of the host Microprocessor component Drosha is decreased during lytic replication and thus allows a shift to the pathway favoring KapB protein production <a href="http://www.plospathogens.org/article/info:doi/10.1371/journal.ppat.1003018#ppat.1003018-Lin3" target="_blank">[104]</a>. On the right, the EBV gene BHRF1 functions as both an mRNA encoding a protein and a pri-miRNA for multiple EBV-encoded miRNAs. During Latency III, Microprocessor binds the transcript and the 5′ translation inhibitory intron is retained in BHRF1 transcripts. Altered transcription start site selection during the lytic cycle results in altered splicing and expression of the BHRF1 protein <a href="http://www.plospathogens.org/article/info:doi/10.1371/journal.ppat.1003018#ppat.1003018-Xing1" target="_blank">[105]</a>. The net result is little BHRF1 protein expression occurs in latency with increased expression during lytic infection. (B) Antisense miRNA/mRNA interactions have been reported in both polyomaviruses and herpesviruses. Viral miRNAs are encoded antisense to viral mRNAs and the viral miRNAs direct siRNA-like cleavage of the mRNAs transcribed in the sense orientation. This antisense arrangement may not only decrease levels of the mRNA but may also serve as a posttranscriptional insulator in <i>cis</i> and <i>trans</i> to prevent the accumulation of long antisense RNAs.