Great regional conference for virologist in the southeast. Abstract due next week.
13.02.2026 15:20
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Great regional conference for virologist in the southeast. Abstract due next week.
"This is pitiful. A thousand people freezing their butts off waiting to worship a rat. What a hype. Groundhog Day used to mean something in this town. They used to pull the hog out, and they used to eat it. You're hypocrites, all of you!"
Our new preprint on #SARSCoV2 nsp14 #exonuclease function in replication fidelity and fitness. ExoN- viruses are attenuated in vitro and in vivo but w/o #interferon signaling replication is largely restored! Suggests nsp14 plays a role in innate antagonism in vivo www.biorxiv.org/content/10.6...
Our paper on the role of #SARSCoV2 NSP3 in stress granule control is now out in JVI.
Reposting our original BioRXIV thread on the summary.
journals.asm.org/doi/10.1128/...
Excellent news. The NIGMS Building Undergraduate Research Training (BURT) T34 NOFO is published. First due is Feb 25th, for December 26 funding. This condenses previous UG NOFOs so reach out to email/previous PO if you have Qs. files.simpler.grants.gov/opportunitie...
The very first @nanoporetech.com MinION library of @themenacherylab.bsky.social at Emory! So far so good! I've been missing Nanopore for a while! Merry Christmas!
🧵 Thread on our new @natcomms.nature.com paper: TLDR -- ADP-ribosylation inhibits viral replication and represents a previously under-appreciated arm of innate immunity during flu infection. Read along for the details…. (1/11) www.nature.com/articles/s41...
When Hannah’s pharmacy began filling her tacrolimus prescription with a generic version, the lung transplant patient didn't know something very important:
Months earlier, an FDA-commissioned study concluded that this generic was not equivalent to the brand drug -- and that her life was at risk.
Put a perspective piece together on how fever may have driven the evolution of antiviral genes: rupress.org/jem/article/...
Frankenstein
Check out @lizthayer.bsky.social's new preprint exploring factors that influence cell-to-cell heterogeneity in interferon (IFN) induction potential!
Are you an early career researcher applying to faculty positions this cycle? My #1 piece of advice is to keep an open mind about what the right department looks like. You might be surprised.
journals.asm.org/doi/10.1128/...
TLDR. #SARS2 NSP15 limits recombination, may play role in viral transcription, and prevents innate immune induction.
Overall, we note:
- CoV recombination occurs at U-rich sites with or without NSP15
- NSP15 mutant has less sgmRNA than WT suggesting role in viral transcription
- NSP15 mutant packages DVGs
- NSP15 regulates rather than promotes recombination
- Selection pressure shapes recombination outcomes.
We think in vivo & in vitro differences governed by selection pressure.
In vitro (most permissive) more recombination observed due to less selection pressure.
In vivo (most restrictive), less overall recombination observe due to selection. Individual abundance suggests more breadth.
Recomibinaton events at d4 represented by a circle for Frequency and its size representing the event's abundance. WT has more events but less individual abundance. Mutant NSP15 has less events but higher abunances.
While we have less recombination in vivo, abundance of individual events increases in the mutant.
To visualize, we plotted each event with a circle and relative abundance by its size.
WT has more events, but lower individual abundances.
NSP15 mutant has less events but higher abundances.
NSP15 has less recombination events in vivo vs WT. SgmRNA still less in mutant as deletions and micro deletions.
What happens in vivo?
Well, not quite what we expected, but interesting.
NSP15 mutant had reduced total recombination vs WT at D2 and D4. Less deletions/microdels.
But we still see less sgmRNA in NSP15 infected lungs.
We also see recombination at U rich sites.
From work by @cblopezlab.bsky.social, Yan Sun, & others, we know DVGs induce strong innate immune responses.
RNA/PFU shifts increases in the NSP15 mutant arguing that DVGs contributing to immune activation.
DVGs and dsRNA likely both play a role in inducing innate immunity with loss of NSP15.
Recombination data from purified virions showing deletions are packaged in the virions and higher in the NSP15 mutant vs WT
Coming back to deletions in the NSP15 mutant, do they get packaged? Yes!
Sucrose cushion purified virions show deletions in viral RNA.
We think the preps are good cause no sgmRNA is packaged.
Thus, the NSP15 mutant produces virions with deletions that may act as defective viral genomes (DVGs)
Data showing the recombination start and stop sites (black WT, red NSP15 mutant). Site of recombination does not change between viruses with and without NSP15
Ok, but does NSP15 impact the sites of recombination? Nope!
Both the WT and mutant still have recombination sites primarily in U rich tracts of RNA.
Results indicate that NSP15 does not facilitate recombination. Instead, it suggest NSP15 protects against increased recombination.
Data shows NSP15 mutant has increased deletions and microdeletion but less sub-genomic RNA
So did the NSP15 mutant reduce recombination? Nope!
Recombination went up in the NSP15 mutant vs WT in cell lysate. We also saw increases in microdeletion & deletions.
Notably, we saw viral sub-genomic message decreased in the mutant. This suggests a role for NSP15 in viral RNA transcription.
We made NSP15 mutant & found attenuation in viral replication & activation of innate immunity.
Results consistent w/ studies on other CoVs & #SARS2 by @profvolkerthiel.bsky.social, Susan Weiss, Benhur Lee, Mohsan Saeed & others.
Studies link NSP15 to controlling viral dsRNA. We don't disagree.
With us being clever, we focus on NSP15, a conserved CoV endoribonuclease that targets U's (EndoU).
EndoU is a known CoV IFN antagonist targeting CoV RNA preventing dsRNA accumulation.
We predicted that it also facilitates recombination by cutting at U-tracts and giving templates to recombine.
Data showing recombination events are increased in SARS2 vs other human coronaviruses
Our sequencing using click chemistry to capture recombination looking for jumps between viral sequences.
Using our approach, we note #SARS2 recombines ~2X more than other CoVs. We have thoughts on why (but not here).
But recombination happens at same spots in all CoV: Uridine (U) rich tracts.
New paper from our lab on CoV recombination in @natcomms.nature.com: www.nature.com/articles/s41...
Collaboration w/ @andrewrouth.bsky.social, the work led by @tommygottago.bsky.social & Yani provides insights into #SARS2 recombination & immune induction.
Some takeaways for the TLDR crowd (1/13)
Results show #SARS2 uses NSP3 at early times to limit SG formation.
Our prior work with N shows antagonism of SGs at late times pubmed.ncbi.nlm.nih.gov/38492217
Coupled with reported anti-SG activities in NSP1 & NSP5, the results show SARS2 invests significant genetic capital in controlling SGs
Our work shows disruption of Y138/F145 disrupts FXR1 binding and attenuates infection both in vitro and in vivo.
Importantly, the NSP3 mutant has no augmentation of type I IFN responses, but is unable to control SG formation after infection and inductions by arsenite.
A new preprint from our group on control of stress granules (SGs) by #SARSCoV2.
Working with Jakob Nilsson's group, we identified key residues in SARS2 NSP3 critical for binding FMRP proteins & disrupting SGs formation.
www.biorxiv.org/content/10.1...
A nice honor to be named to Clarivate’s Highly Cited Researchers for 2025.
The recognition is a testament to all the hard work my research group and our collaborators have done over the years.
news.emory.edu/stories/2025...