Uncovering the structure of the poxvirus 'portal complex'
Poxviruses have a long history in human disease as well as medicine: The first-ever vaccine was developed to protect against smallpox, which has since been eradicated. Despite this, scientists still don't fully understand how poxviruses infect and replicate inside our cells. Recent outbreaks of mpox highlight an urgent need to better understand poxvirus biology.
Peter Rosenthal leads the Structural Biology of Cells and Viruses Laboratory at the Crick, seeking to understand the 3D structures of viruses, often focusing on viruses such as influenza. "Poxviruses are bigger and have many more components. We've needed new methods to understand their organization," he says.
Rosenthal recently joined forces with Michael Way, head of the Crick's Cellular Signaling and Cytoskeletal Function Laboratory, who focuses on how the vaccinia poxvirus hijacks human cells. Both were interested in how poxviruses release genetic material and assemble new viruses.
"At the start of infection, poxviruses release their genetic material in two steps from their sealed viral core into the host cell," says Way. "First, messenger RNA transcripts are exported to produce proteins that suppress the host's immune and antiviral response, followed by the virus's DNA genome to allow replication of new viruses."
The exit channel
Until now, researchers didn't know how any genetic material was released from the viral core. But they had identified channels embedded in the wall of the viral core, dubbed "portal complexes," suspected to play a role in transporting the viral genetic material, like a molecular exit tunnel.
In a study published in Nature, Tom Calcraft in Rosenthal's lab worked with Miguel Hernandez Gonzalez in Way's lab to determine the structure of the portal complex using cryo-electron tomography, a rapidly advancing technique that allows imaging of more complicated structures at higher resolution.
"This powerful imaging technique gave us a 'map' of the portal complex, essentially a sketch of the different components that make up the core and all the structures surrounding it," says Calcraft.
A molecular jigsaw puzzle
Calcraft and Hernandez Gonzalez then used the AI software AlphaFold2 to predict the structures of all known proteins in the vaccinia virus. Each potential protein was then slotted into the portal map to see which best matched.
"We identified three crucial proteins that make up the portal complex," says Hernandez Gonzalez. "They're all previously known to be essential for mRNA export, and one is also involved in the assembly of new virus particles, showing how critical portal complexes are to the virus."
The study also showed how a viral enzyme responsible for the release of the DNA genome docks onto the portal complex. "This was so exciting: It was evidence that the portal complex works like a central hub, connecting core functions in the virus replication cycle," says Calcraft.
"We'd known about these three proteins in isolation, but no one had expected them to work together like this," adds Rosenthal. "AI prediction tools allowed us to be less restrictive with our assumptions and, combined with more powerful imaging techniques, completely opened up our view of this group of important viruses."
Potential for new therapeutic targets
The portals must efficiently export large amounts of genetic material, but the virus's reliance on this transportation channel could help stop it in its tracks.
Way adds, "We now have a structural target to focus on. And because poxviruses are so similar, they will have similar portal complexes, so the same drug could work on different members of this virus family."
Now leading a lab at the Pirbright Institute, Hernandez Gonzalez is continuing his collaboration with Rosenthal's team to better understand how the genetic material is being transported through the portals. Their research will involve screening for potential drugs that could block the release of the genetic material, aiming to get closer to new treatment strategies.
Publication details
Thomas Calcraft et al, In situ structure of the poxvirus portal complex, Nature (2026). DOI: 10.1038/s41586-026-10856-2
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Citation: Uncovering the structure of the poxvirus 'portal complex' (2026, July 30) retrieved 30 July 2026 from https://phys.org/news/2026-07-uncovering-poxvirus-portal-complex.html
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