And now the peer-reviewed published paper!! Open access for the final version. academic.oup.com/nar/advance-... Thanks again
Hutchinson, Brooke and Russell labs.

Fancy QR link 9/9

This work was led by Jordan Ranum and Mitch Ledwith, with really fruitful collaborations with the Brooke, Russell and Hutchison labs. 8/9

PB2 DPRs reduce polymerase activity, suppress viral infection, and act in trans to inhibit replication of WT virus. We argue that DelVGs pack a one-two punch – both the RNA itself and the encoded DPR combine to antagonize WT virus. 7/9

DPRs dramatically expand the coding space of RNA viruses. We characterized DPRs made from the polymerase subunit PB2, revealing that they are dominant negative inhibitors of polymerase assembly. 6/9

…an entirely new class of protein expressed from DelVGs. We show that DelVGs are translated, producing hundreds of cryptic proteins we called DPRs (DelVG-encoded PRotein). DPRs include proteins with large internal deletions, as well as protein deletions that shift into alternative reading frames.5/9

Part of this inhibition comes from the DelVG RNA itself; they compete with their full-length counterparts for replication, directly interfering with replication. DelVG RNAs can also activate antiviral responses that indirectly inhibit WT virus. Our preprint reveals another key player in this battle…

These mistake result in point mutations. Almost all RNA viruses also make much larger mistakes, creating genomes with large internal deletions. These deletion-containing viral genomes (DelVGs) parasitize WT virus for their own propagation, and in the process poison replication of WT virus. 3/9

RNA viruses face a race against the clock. They must get in and out of cells before antiviral forces stop them. This prioritizes speed. But this need for speed comes at a cost – fidelity is sacrificed as the genome is copied quickly by the viral RNA-dependent RNA polymerase. 2/9