Skip to main content

Write a PREreview

Cryptic proteins translated from deletion-containing viral genomes dramatically expand the influenza virus proteome

Posted
Server
bioRxiv
DOI
10.1101/2023.12.12.570638

Productive infections by RNA viruses require faithful replication of the entire genome. Yet many RNA viruses also produce deletion-containing viral genomes (DelVGs), aberrant replication products with large internal deletions. DelVGs interfere with the replication of wild-type virus and their presence in patients is associated with better clinical outcomes as they. The DelVG RNA itself is hypothesized to confer this interfering activity. DelVGs antagonize replication by out-competing the full-length genome and triggering innate immune responses. Here, we identify an additionally inhibitory mechanism mediated by a new class of viral proteins encoded by DelVGs. We identified hundreds of cryptic viral proteins translated from DelVGs. TheseDelVG-encodedproteins (DPRs) include canonical viral proteins with large internal deletions, as well as proteins with novel C-termini translated from alternative reading frames. Many DPRs retain functional domains shared with their full-length counterparts, suggesting they may have activity during infection. Mechanistic studies of DPRs derived from the influenza virus protein PB2 showed that they poison replication of wild-type virus by acting as dominant-negative inhibitors of the viral polymerase. These findings reveal that DelVGs have a dual inhibitory mechanism, acting at both the RNA and protein level. They further show that DPRs have the potential to dramatically expand the functional proteomes of diverse RNA viruses.

You can write a PREreview of Cryptic proteins translated from deletion-containing viral genomes dramatically expand the influenza virus proteome. A PREreview is a review of a preprint and can vary from a few sentences to a lengthy report, similar to a journal-organized peer-review report.

Before you start

We will ask you to log in with your ORCID iD. If you don’t have an iD, you can create one.

What is an ORCID iD?

An ORCID iD is a unique identifier that distinguishes you from everyone with the same or similar name.

Start now