Baker Lab | Lovelace Biomedical | ABQ, NM
Influenza and alternative RNA splicing
Steve Baker
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Seminal work by Lenschow, Krug, and Bogunovic found that ISG15 is antiviral against influenza A and B virus in mice, but in humans ISG15 antagonizes influenza B virus and less so A. This is in part explained by ISG15’s ability to dampen inflammation 3/4
Non-canonical ISG15 (ncISG15) encodes an 8 aa N-terminal truncation. Like ISG15 it post-translationally modifies proteins and is secreted, but ISG15 is 100X more abundant (explaining its lack of ID). Things got spicy when we tested ncISG15’s function during influenza A viral infection 2/4
Now live! Nearly all human genes contain multiple transcript isoforms - and the genes that predominantly control infection, ISGs, are no different. Using PacBio with analysis help from Yan Guo, Himadri noticed a never-before-seen transcript isoform of ISG15 that potently restricts flu 1/4
Proud to be in a class with some seriously impressive up-and-comers. Inaugural class here: journals.asm.org/journal/jvi/...
I'll be penning an article with colleague and friend @hanckslab.bsky.social on mitochondrial proteins that moonlight to execute immune responses
@jvico-eics.bsky.social
Using transcript-aware knockdown we found that endogenous ncISG15, and not ISG15, is antiviral against influenza A virus through polymerase restriction. But life finds a way, and influenza A NS1 antagonizes ncISG15. ncISG15 seems widely conserved- we’re excited how this finding shapes the field! 4/4
Cryo-EM structure reveals how influenza A virus NEP binds the viral polymerase at a regulatory hotspot, coordinating RNA synthesis and nuclear export. Fantastic collaboration with @loiccarrique.bsky.social and Jon Grimes. www.science.org/doi/10.1126/...
Excited to share our work on #AncientRNA from alcohol-preserved lungs, recovering the oldest human RNA virus genome (an 18th-century rhinovirus). Our study shows that viral RNA remnants persist in centuries-old tissue, opening new ways to study virus evolution and historical disease #Paleovirology🫁🦠
Ever wondered how fever helps fight flu? Our research shows that fever-like temperature tip the scales in the battle between the influenza virus and the immune system by enhancing antiviral responses and altering viral RNA dynamics. Check out the full article here:
www.science.org/doi/10.1126/...
Very happy to have been able to contribute to this study that was published today in Science, which was truly a great collaborative effort. Avian PB1 provides a fitness advantage to IAV at febrile-range temperatures both in vitro and a hyperthermic nouse model 🦠 www.science.org/doi/10.1126/...
#flu
On the second day of Christmas, a virus gave to me…
