Dear TWIV Team,
As a long time listener and fan of your podcast, I was happy to hear that one of the topics covered in episode 216 was splicing. Splicing, as you discussed, is an important process that can create diversity in many genes. However, I also wanted to point out that splicing can help viruses ‘keep track of the time’. This is the conclusion of my recent manuscript published in Cell’s new open access journal – Cell Reports (http://www.cell.com/cell-reports/fulltext/S2211-1247%2812%2900454-8). The manuscript describes how the complex timing of flu can be coordinated with only a few components. In short, a poor splice site in NS1 results in the slow accumulation of NEP – the nuclear export protein. As NEP accumulates over time, the virus switches from transcription to replication and packaging. The mechanism is both simple and incredibly elegant.
In studying the relationship between NS1, the interferon antagonist, and its spliced partner, NEP, I found that NEP levels are more essential to influenza virus replication than those of NS1. Decreasing NS1 levels to greater than 80% by miRNA targeting had no detrimental effect on virus replication or its ability to antagonize the cell’s response to infection. Given the fact that it was unlikely that a virus would waste such resources, I instead focused on NEP, as the balance between these two proteins are linked by splicing (for every 10 NS transcripts, the virus makes ~1 NEP transcript). To this end, I found that altering levels of NEP had a dramatic impact on viral fitness. Altogether I propose that the slow accumulation of NEP during virus replication, coordinates the timing of the overall infection, providing influenza with a ‘molecular timer’.
This work is receiving a lot of public interest (see below) but none of these stories cover the real science in the paper which I am very proud of. In any regard, I thought I would bring this unique utilization of splicing to your attention.
I thank you for your time and, as always, look forward to the next podcast.
Reported stories on this work include:
Hello Esteemed Twivvers!
Thanks as always for a great and enlightening podcast.
I have a couple of questions about the flu vaccine after reading Helen Branswell’s interesting article today–How is it that a flu vaccine can be a “good match” for the circulating flu but only have an efficacy of 55%? Shouldn’t a good match be much closer? Also, it is always said that even if the vaccine is not a good match, you can still get “some protection” and your flu won’t be as bad. What is the mechanism of action? I very much believe that the flu vaccine as it is is way better than nothing at all and always get my flu shot, but I would love to be able to answer these questions.
So, if it’s the detergents and formaldehyde that coat the proteins (H and N?), changing the presenting antigen structure, does that mean that this new vaccine process, Flublok, will be more effective? It looks as though they are having bacteria (or something) churn out hemagglutinin particles. Presumably as they are churned out, they are not being coated with anything? It seems then that that might be a more true-to-life antigen. Also, as a side note, do we know which hemagglutinin Flublok has? That is, I remember reading in a previous Virology 101 that you wrote that there were multiple types of H protein, thus the H1 or H3 etc. Does Flublok have just one subtype of H or multiples? Could this be the first step to a universal vaccine if one could put all the H subtypes into one vaccine?
So many questions, but this stuff is really cool!
Here’s a topic you may want to discuss on the blog or TWIV: The new flu vaccine that was approved yesterday by the FDA. According to the press releases it’s the first recombinant subunit flu vaccine (no live influenza used) and it’s the first egg-free vaccine (not sure if this is still true though) .
My disclaimer: I cut my virology teeth on the baculovirus system (worked with George Rohrmann at Oregon State), so this is exciting news for all baculovirologists. It’s great to see the insect expression system make it all the way to FDA approval with this vaccine.
Thanks for all your work on the Virology blog. I teach Virology at a small college in Arkansas and your blog is a great resource.
Keep up the great work
Dept. of Biology
John Brown University
Hi Vincent & Team,
hear are some nice virus sculptures: http://imgur.com/a/XpU18
Hi TWiV team-
I am a longtime listener and fan, and just wanted to share this really cool art with you. These are some fantastic glass renditions of various viruses and some bacteria. Perhaps a listener pick of the week?
Thanks for the great podcast,
Good morning. I was just looking through imgur.com and stumbled upon this. It is from artist Luke Jerram who makes glass replicas of viruses, bacteria and other pathogens. Thought you might like to take a look, and perhaps showcase the artist as a pick of the week some time.
Here’s the imgur link: http://imgur.com/gallery/XpU18
and here’s the artist’s website: