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UK Health Security Agency | Evidence gap map Oropouche Virus

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Stephen Graham's Lab @atomicvirology.bsky.social · Aug 14

They even made an interactive evidence map:
research.ukhsa.gov.uk/evidence-gap...

Particularly relevant on a day when the first reports have emerged of imported Oropouche cases in the UK:
www.gov.uk/government/n...

research.ukhsa.gov.uk

Oropouche virus: a rapid evidence gap map

Stephen Graham's Lab @atomicvirology.bsky.social · Aug 14

#Oropouche virus news!! @ukhsa.bsky.social has mapped the evidence for Oropouche virus epidemiology, vectors and ecology, virology, pathogenesis, medical countermeasures and public health:
www.gov.uk/government/p...

An incredibly useful resource to guide future research and funding

This rapid evidence gap map identifies and categorises the available evidence on Oropouche virus to inform research prioritisation.

www.gov.uk

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Stephen Graham's Lab @atomicvirology.bsky.social · Aug 11

Now published in @embomolmed.org 🥳🎉
Protein-based tools for detection and characterisation of #Oropouche virus infection...
See the final paper at doi.org/10.1038/s443... and read the bluetorial 👇

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Stephen Graham's Lab @atomicvirology.bsky.social · Aug 9

It's a lie....🤫

Stephen Graham's Lab @atomicvirology.bsky.social · Aug 9

Fridge is stacked, marquee is up, house didn't need cleaning because it's always super tidy...😬🤥
I think we're ready for the lab summer garden party!

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Stephen Graham's Lab @atomicvirology.bsky.social · Jul 27

Great job @danielacl.bsky.social presenting this work at #IHW2025. Missed the talk? You can still catch her at poster 3.14 this evening!

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Stephen Graham's Lab @atomicvirology.bsky.social · Jul 27

Want to know more? Come to the talk by @danielacl.bsky.social today at #IHW2025 (room 2 at 11:39) or come to her poster tonight (number 3.14).

a man in a tuxedo is applauding in front of a crowd of people

Stephen Graham's Lab @atomicvirology.bsky.social · Jul 27

Congratulations to primary authors Holly and @danielacl.bsky.social on their first first-author research papers. This work was a fun collaboration with @deanelab.bsky.social, and many thanks to @bsfcharity.bsky.social for funding.

ALT: a man in a tuxedo is applauding in front of a crowd of people

media.tenor.com

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Stephen Graham's Lab @atomicvirology.bsky.social · Jul 27

While pUL21 doesn’t bind a new surface on PP1, so no new antiviral drugs 😢, we have identified a new mode of PP1 binding via an extended beta sheet…this binding of a protein with no canonical SLiMs to PP1 suggests there might be many more PP1 adaptors in the cell than previously suggested.

a cartoon of a wizard with the words you 've come to the right place

Stephen Graham's Lab @atomicvirology.bsky.social · Jul 27

Why would a virus keep a suboptimal RVxF motif rather than evolve higher affinity? We hypothesise that it is an additional layer of regulation, make sure that PP1 recruitment only happens in the right place, and at the right time post-infection, when local concentrations of pUL21/pORF38 are high.

ALT: a cartoon of a wizard with the words you 've come to the right place

media.tenor.com

Stephen Graham's Lab @atomicvirology.bsky.social · Jul 27

However, the affinity of pORF38 for PP1 is ~10-fold lower than for some cellular PP1 binders. This is because these pUL21 and pORF38 residues structurally corresponding to the RVxF motif have non-optimal sequences. Mutating these residues to make a canonical RVxF motif enhances PP1 binding.

Stephen Graham's Lab @atomicvirology.bsky.social · Jul 27

Using fluorescence polarization, we showed the TROPPO peptide alone is not enough to bind PP1, you need the whole protein. Also, we show that VZV pORF38 directly competes with cellular RVxF+ϕϕ[xF] motif containing peptides for binding the RVxF motif.

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Stephen Graham's Lab @atomicvirology.bsky.social · Jul 27

This explains why deleting a chunk of the linker between the pUL21 N-terminal domain (NTD) and the TROPPO motifs abolishes PP1 binding, why our previous TROPPO mutations prevent binding (they would block packing of the TROPPO and the pUL21 NTD), and new mutations further supported the #AF3 models.

Stephen Graham's Lab @atomicvirology.bsky.social · Jul 27

Using #AlphaFold3, we predicted the structure of HSV-1 pUL21 and VZV pORF38 in complex with PP1. Surprisingly, the TROPPO motif binds the same hydrophobic groove as cellular RVxF and ϕϕ[xF] motifs. Strikingly, a disordered linker region of pUL21 is predicted to become ordered upon PP1 binding.

a close up of a man wearing glasses and a wig .

Stephen Graham's Lab @atomicvirology.bsky.social · Jul 27

This TROPPO motif is conserved across the alphaherpesviruses, but it doesn’t resemble any of the known PP1 binding motifs (RVxF, SILK, ϕϕ[xF], etc.). Does that mean pUL21 and homologues bind PP1 via a novel surface, that could be targeted with antiviral drugs?

ALT: a close up of a man wearing glasses and a wig .

media.tenor.com

Stephen Graham's Lab @atomicvirology.bsky.social · Jul 27

We showed a few years ago that HSV pUL21 is a PP1 adaptor protein, directing dephosphorylation of cellular and viral proteins, and that PP1 recruitment requires a novel motif: TROPPO (a tenuous bacronym 😉)

Alphaherpesvirus pUL21 homologues use non-canonical motifs to compete with cellular adaptors for protein phosphatase 1 binding

Stephen Graham's Lab @atomicvirology.bsky.social · Jul 27

How does #herpes hijack a human phosphatase to promote virus replication? We have a new @biorxivpreprint.bsky.social preprint showing how #HSV and #VZV use a novel motif to compete with canonical cellular #PP1 adaptors.
www.biorxiv.org/content/10.1...
🧵👇

Protein phosphatase 1 (PP1) is a key regulator of cellular phosphorylation and its activity is regulated via binding to cellular regulatory proteins via conserved short linear motifs (SLiMs). The herp...

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Stephen Graham's Lab @atomicvirology.bsky.social · Jul 26

Barnstorming talk by @danandviruses.bsky.social on his work looking at HSV infection is neurons and its ability to alter neuronal firing 💯👏
Missed the talk? You can still catch Dan at his poster tomorrow night (3.59). #IHW2025

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Stephen Graham's Lab @atomicvirology.bsky.social · Jul 25

We made it #berlin #IHW2025

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Stephen Graham's Lab @atomicvirology.bsky.social · Jul 25

7:30 am is a touch too early for that, even by my louche standards!

A new protein-dependent riboswitch activates ribosomal frameshifting

Stephen Graham's Lab @atomicvirology.bsky.social · Jul 25

It's time! The atomic virology team are on their way to Berlin for #IHW2025

Lab at the airport in front of an entirely reputable restaurant for a morning breakfast when traveling...

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Stephen Graham's Lab @atomicvirology.bsky.social · Jul 20

Do viruses control protein translation using riboswitches? Via protein-mediated regulation of -1 programmed ribosomal frameshifting? We think the do. Very happy to have played a (small) part in this epic paper by @jemmabetts.bsky.social, @chillzaa.bsky.social and colleagues. See 👇for bluetorial.

Chris H. Hill @chillzaa.bsky.social · Jul 19

New preprint alert! 🚨👇 I'm delighted to share the latest research from @jemmabetts.bsky.social
in our group: ‘A new protein-dependent riboswitch activates ribosomal frameshifting’. Huge congratulations to Jemma for the first manuscript of her PhD! ✨

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

Programmed -1 ribosomal frameshifting (PRF) is a ubiquitous translational control mechanism in RNA viruses, allowing them to change the relative abundance of proteins encoded in different reading fram...

A new protein-dependent riboswitch activates ribosomal frameshifting

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Reposted by Stephen Graham's Lab

Chris H. Hill @chillzaa.bsky.social · Jul 19

New preprint alert! 🚨👇 I'm delighted to share the latest research from @jemmabetts.bsky.social
in our group: ‘A new protein-dependent riboswitch activates ribosomal frameshifting’. Huge congratulations to Jemma for the first manuscript of her PhD! ✨

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

Programmed -1 ribosomal frameshifting (PRF) is a ubiquitous translational control mechanism in RNA viruses, allowing them to change the relative abundance of proteins encoded in different reading fram...