Max Fels
@mfels.bsky.social
74 followers 140 following 13 posts
Branco Weiss and Moderna Global Fellow at DFCI/HMS. On the lookout for the strangest viruses out there. https://brancoweissfellowship.org/fellow/fels/
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mfels.bsky.social
I’m grateful to everyone who worked on this project with me–Aidan, Richard, @yoitsjasmine.bsky.social , @molbiolgv.bsky.social , and Chantal. As always, huge thanks to @kranzuschlab.bsky.social and Amy for making it possible for me to work on these kinds of questions!
mfels.bsky.social
This unique viral replication strategy shows that you can build sophisticated translation regulation through a very simple cap-binding complex. Perhaps there are contexts in which cellular organisms also make use of similar strategies?
A model of the function of viral IF4F.
mfels.bsky.social
But why do these viruses not just rely on the host cap-binding complex? We found that mimivirus replication is unusually resistant to abiotic stresses in a way that depends on viral translation factors. Could it be an adaptation to the unusual stresses faced by the amoeba host?
mfels.bsky.social
How does the viral cap-binding complex specifically promote viral translation? Viral mRNAs carry a unique 5′ UTR motif: a conserved +1A followed by AU-rich sequences. A crystal structure of vIF4E shows exactly how this mRNA cap is recognized!
Crystal structure of viral IF4E bound to a viral cap structure.
mfels.bsky.social
This effect becomes obvious when looking at viral factories by TEM. Early in infection these large structures form independent of the viral cap-binding complex, but when this complex is disrupted viral particles cannot assemble.
Transmission electron micrograph showing viral factories in amoebae infected with mimivirus.
mfels.bsky.social
We call these proteins viral IF4A, IF4E, and IF4G. They 1) form a complex, 2) are essential for viral replication, and 3) act as bona fide translation factors, promoting synthesis of viral structural proteins late in infection.
mfels.bsky.social
In amoeba infected by mimivirus, the prototypical giant DNA virus, we found dozens of viral proteins bound to ribosomes—including three that are homologous to the eukaryotic mRNA cap-binding complex (eIF4A, eIF4E, eIF4G).
mfels.bsky.social
Giant DNA viruses encode a stunning number of proteins that were long thought unique to living organisms. Among them: translation factors, the master regulators of protein synthesis. But are these viral proteins functional?
Transmission electron micrograph of a mimivirus particle.
Reposted by Max Fels
kranzuschlab.bsky.social
>18,000 new genomes of giant DNA viruses! An incredible trove of new genes and insights into evolution of host-virus interactions from @fmschu.bsky.social and @jgi.doe.gov

www.biorxiv.org/content/10.1...
mfels.bsky.social
Congrats! Beautiful work
mfels.bsky.social
Shameful. Sorry Jason!
mfels.bsky.social
Cool work! Will you add phages or viruses of the rest of eukaryotes?