Julie Pfeiffer

Very proud to have our lab’s first work published in @cp-cellhostmicrobe.bsky.social!

In this work, we use functional metagenomics to find phage defenses from human and soil microbiomes!

Congrats to first author @luis840alberto.bsky.social !

www.cell.com/cell-host-mi...

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Exciting news: Carla Saleh is now Chair of Virology at Pasteur! Congrats to Carla and all who will benefit from her exceptional leadership!

After defending her Ph.D. thesis Valerie hits the "EASY" button, which says, "that was easy". She celebrates.

Finally, huge congrats to Valerie on this story, which spanned virology, genetics, cell biology, biochemistry, and mouse infections (thanks to @robertmaples.bsky.social‬ for help with mouse work!). She defended her thesis last week and will start a postdoc with @msdiamondlab.bsky.social‬ soon! 10/10

Thanks to the reviewers and editor Ken Cadwell for their very helpful/constructive comments that improved our paper. Their reviews and our responses are available here under the Peer Review tab: journals.plos.org/plosbiology/... 9/10

This story illustrates why we love forward genetic approaches in virology—they reveal unanticipated facets of replication. In a system where any mutation that increases early progeny could be selected, the fact that an egress-enhancing mutation emerged highlights the inefficiency of MNV egress. 8/10

We don’t know. But it could be: 1) Early cell death reduces total viral yield in the long run. Indeed, we found that WT “catches up” over a full 16 hour single cycle of infection, 2) Early progeny release induces early host immune responses, 3) K40R viruses could have transmission defects. 7/10

Does NS3-K40R suffer a fitness cost in mice—a complex environment with more selective pressure? Nope. At least not in our relatively short-term infection experiments. So why doesn’t WT virus have arginine at position 40? (Fun fact: human Norwalk virus DOES have arginine at this position.) 6/10

Instead, NS3-K40R viruses have faster egress from cells due to earlier mitochondrial disruption and cell death. In spite of this conservative amino acid change, NS3 protein containing K40R disrupted liposomes that mimic mitochondrial membranes at concentrations 10-100 fold lower than WT NS3. 5/10

She identified a mutation in the N terminal domain of NS3—K40R—that was sufficient to increase replication speed. Curiously, the mutation did not alter RNA replication or NTPase activity, two other important functions of NS3. 4/10

But we didn’t know that when Valerie started her project in 2021. To identify inefficiencies in replication, she used a forward genetic approach to enrich for MNV variants that replicate faster, by collecting the very earliest progeny. (We had IBC approval in advance!) 3/10

In 2023 our colleagues ‪@tiffanyreeselab.bsky.social‬ & @hanckslab.bsky.social‬ showed MNV egress requires viral NS3, which disrupts mitochondria to induce cell lysis. Without this function of NS3, cells become bags of viruses that can’t escape. 2/10 www.nature.com/articles/s41...

Drawing of a cell showing mitochondria in the cytoplasm, with murine norovirus virions exiting the cell through damage to the plasma membrane. Image credit: Valerie Rodriguez Irizarry

Photo of Valerie Rodriguez Irizarry

Valerie Rodriguez Irizarry’s tour de force paper on murine norovirus adaptation/egress is now out in peer-reviewed form ‪@plosbiology.org‬. It highlights the power of forward genetics in virology research. 🧵 1/10 journals.plos.org/plosbiology/...

Terrence S. Dermody and Julie K. Pfeiffer: To tackle chronic disease, turn to the virologists Despite the United States being a global leader in many areas, Americans are not healthy. Life expectancy is lower than in other industrialized nations,...

Terry Dermody and I wrote an op-ed about chronic diseases ("Make America Healthy Again"), the role of viral infections, and how virologists can help. www.post-gazette.com/opinion/gues...

🚨 New paper out!
"A single mutation in an enteric virus alters tropism and sensitivity to microbiota"
One tiny change, big consequences.
A great collab with the Julie Pfeiffer lab! @jkpfeiff.bsky.social
Read here: bit.ly/42sD2rX
#Virology #Microbiome #Science

Functional Metagenomic Selections for Phage Defense

My lab’s first preprint!

We used functional metagenomics to identify phage defenses in human and soil microbiomes. We scaled these selections while maintaining accuracy, enabling us to examine 9 habitats for defense elements against 7 phages.

www.biorxiv.org/content/10.1...

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An extremely talented female scientist smiles.

New preprint from Valerie Rodriguez-Irizarry in our group-- her tour de force thesis work used forward genetics to discover new insights into non-enveloped viral egress.
www.biorxiv.org/content/10.1...

chalk + chalkboard with diagrams

lab group silly picture

Wow - bluesky! 📈 🦠

Please help me amplify a special faculty search. We're looking for someone in "Microbial Systems Biology" to join me and @kreynoldslab.bsky.social at UTSW Sys Bio / Bioinformatics.

There is an empty lab space right next to us waiting for you!

apply.interfolio.com/154339

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Microbiology Department potluck lunch ✨

Happy halloween.

This Saturday on the Yale campus Nobel laureate Charlie Rice will lecture in honor of Dr. Brett Lindenbach. A link for seeing the event remotely is below. A chance to celebrate all the wonderful professional and personal connections many of us have with Brett. yale.hosted.panopto.com/Panopto/Page...

Wonderful to celebrate the legacy of Beth Levine yesterday. Dr. Noboru Mizushima, first winner of the Beth Levine M.D. Prize in Autophagy Research, gave a fantastic seminar including amazing drawings of his history with Beth. www.utsouthwestern.edu/research/bet....

Wow, it's so much nicer over here.