Viral RNA Modulation of Host Gene Expression – Discovery and Innovation at University of Utah Health

Model of viral HSUR2 RNA function. HSUR2 base-pairs with both host target mRNAs and miRNAs (miR-142-3p and miR-16), tethering them together and inhibiting target mRNA stability and expression.

Viruses depend on and modulate their hosts’ cellular environments to maximize replication. Studies of viruses can therefore reveal important aspects of host-pathogen interactions and fundamental cell biology. Viruses often modulate host pathways using proteins, but can also express non-coding RNAs whose functions and mechanisms are mostly unknown.

Cazalla and colleagues studied the small RNAs from H. saimiri, a herpesvirus that establishes latency in the T cells of New World primates and can cause aggressive leukemias and lymphomas in non-natural hosts. They showed these RNAs, called HSURs, modulate host gene expression and inhibit host cell death using a novel mechanism in which the HSURs inhibit host mRNAs by tethering them to host miRNAs and the associated degradation and translation inhibition machinery. This mechanism is a completely novel process, not previously observed in cells, and but which promises to lead to a fuller understanding of gene regulation in both infected and uninfected cells.