Good news! Defeating viral pathogens one trick at a time!
Seems to be an impressive study!
"... The two main viruses that cause the flu — influenza A and B — have existed for centuries and, although some antiviral advances have been made, these bugs have proven extremely difficult to eradicate. ...
The finding hinges on understanding how the virus is able to wield a protein known as PA-X to make myriad cuts in the RNA of host cells without harming its own RNA.
When the flu bug uses this protein to slice up the RNA in its host, it is able to [prevent] the RNA from doing one of its key jobs when it comes to infections – triggering the immune system to fight the bug. It also allows the virus to take over the host cell and create copies of itself in a process known as host shutoff. Yet, somehow the protein doesn't affect the virus' own RNA.
What the researchers found is that the RNA sequence targeted by PA-X is extremely specific. In fact, it's one that exists in abundance in humans and other animals susceptible to infection by the virus, but one that is barely found in the virus' own RNA. ...
an ability that's not been seen in viruses before called self/non-self recognition. It refers to a mechanism by which the virus can differentiate between its own RNA and that of its host. While it's been seen in reverse – host cells being able to tell the difference between themselves and viruses – knowing that the virus itself can do it is new information. ..."
The finding hinges on understanding how the virus is able to wield a protein known as PA-X to make myriad cuts in the RNA of host cells without harming its own RNA.
When the flu bug uses this protein to slice up the RNA in its host, it is able to [prevent] the RNA from doing one of its key jobs when it comes to infections – triggering the immune system to fight the bug. It also allows the virus to take over the host cell and create copies of itself in a process known as host shutoff. Yet, somehow the protein doesn't affect the virus' own RNA.
What the researchers found is that the RNA sequence targeted by PA-X is extremely specific. In fact, it's one that exists in abundance in humans and other animals susceptible to infection by the virus, but one that is barely found in the virus' own RNA. ...
an ability that's not been seen in viruses before called self/non-self recognition. It refers to a mechanism by which the virus can differentiate between its own RNA and that of its host. While it's been seen in reverse – host cells being able to tell the difference between themselves and viruses – knowing that the virus itself can do it is new information. ..."
From the abstract:
"Many viruses block host gene expression to take over the infected cell. This process, termed host shutoff, is thought to promote viral replication by preventing antiviral responses and redirecting cellular resources to viral processes. Several viruses from divergent families accomplish host shutoff through RNA degradation by endoribonucleases. However, viruses also need to ensure expression of their own genes. The influenza A virus endoribonuclease PA-X solves this problem by sparing viral mRNAs and some host RNAs necessary for viral replication. To understand how PA-X distinguishes between RNAs, we characterized PA-X cut sites transcriptome-wide using 5' rapid amplification of complementary DNA ends coupled to high-throughput sequencing. This analysis, along with RNA structure predictions and validation experiments using reporters, shows that PA-Xs from multiple influenza strains preferentially cleave RNAs at GCUG tetramers in hairpin loops. Importantly, GCUG tetramers are enriched in the human but not the influenza transcriptome. Moreover, optimal PA-X cut sites inserted in the influenza A virus genome are quickly selected against during viral replication in cells. This finding suggests that PA-X evolved these cleavage characteristics to preferentially target host over viral mRNAs in a manner reminiscent of cellular self versus non-self discrimination."
Cut site preference allows influenza A virus PA-X to discriminate between host and viral mRNAs (no public access, but here is the link to the biorxiv preprint)
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