Alexander Robertson
@alexrob.bsky.social
PhD candidate at UW Seattle. I study how interactions between viruses shapes their evolution. Also 📷, 🎹, 📽️, 🐦
Ahh, that makes so much sense! Thanks for such a thoughtful response and again, really interesting paper!
December 11, 2025 at 1:44 AM
Ahh, that makes so much sense! Thanks for such a thoughtful response and again, really interesting paper!
Really cool work! Maybe a naive question but I was curious--do you think that this holds for multicellular organisms that can "replicate" via regeneration? I'm thinking of how worms, starfish, some plants, etc. can be cut into pieces and how each piece could regenerate into a new organism.
December 10, 2025 at 10:55 PM
Really cool work! Maybe a naive question but I was curious--do you think that this holds for multicellular organisms that can "replicate" via regeneration? I'm thinking of how worms, starfish, some plants, etc. can be cut into pieces and how each piece could regenerate into a new organism.
If you’re interested in antiviral design, viral evolution, eco-evolutionary feedbacks, ploidy, etc. etc. etc., drop me a line! Also, check out this nice press release that UW news wrote about the paper: newsroom.uw.edu/news-release...
December 8, 2025 at 5:15 PM
If you’re interested in antiviral design, viral evolution, eco-evolutionary feedbacks, ploidy, etc. etc. etc., drop me a line! Also, check out this nice press release that UW news wrote about the paper: newsroom.uw.edu/news-release...
Big picture: the feedback loop between viral density leading to social interaction, which leads to realized phenotype, which alters fitness, leading to new viral densities, should be considered when designing optimal treatments.
December 8, 2025 at 5:15 PM
Big picture: the feedback loop between viral density leading to social interaction, which leads to realized phenotype, which alters fitness, leading to new viral densities, should be considered when designing optimal treatments.
Perhaps the most interesting thing to me is that this parallels recent work which frames viral infection in the terms of ploidy. What are the dis/advantages of having a “non-fixed ploidy”? How can broadening our understanding of population genetics lead to better pathogen treatments?
December 8, 2025 at 5:15 PM
Perhaps the most interesting thing to me is that this parallels recent work which frames viral infection in the terms of ploidy. What are the dis/advantages of having a “non-fixed ploidy”? How can broadening our understanding of population genetics lead to better pathogen treatments?
These ideas, which seem counterintuitive, have actually been described for therapies that treat cancers and bacteria. Similar ideas have also been proposed for the use of therapeutic interfering particles (TIPs).
December 8, 2025 at 5:15 PM
These ideas, which seem counterintuitive, have actually been described for therapies that treat cancers and bacteria. Similar ideas have also been proposed for the use of therapeutic interfering particles (TIPs).
This isn’t a clinical recommendation (!!!) but it highlights a very important consideration for antivirals that depend on virus-virus interactions: they must balance killing viruses 𝘯𝘰𝘸 with preserving the interactions that keep resistance low 𝘭𝘢𝘵𝘦𝘳.
December 8, 2025 at 5:15 PM
This isn’t a clinical recommendation (!!!) but it highlights a very important consideration for antivirals that depend on virus-virus interactions: they must balance killing viruses 𝘯𝘰𝘸 with preserving the interactions that keep resistance low 𝘭𝘢𝘵𝘦𝘳.
When we simulated clinical trials using weaker drugs, they cleared later on average (mostly due to fewer early clearers). But the overall viral load was lower in the x100 group, and resistance frequency was likewise reduced.
December 8, 2025 at 5:15 PM
When we simulated clinical trials using weaker drugs, they cleared later on average (mostly due to fewer early clearers). But the overall viral load was lower in the x100 group, and resistance frequency was likewise reduced.
Counterintuitively, our model suggests that a weaker treatment may maintain enough coinfection to keep resistant viruses wrapped in susceptible capsids, while still maintaining low viral load.
December 8, 2025 at 5:15 PM
Counterintuitively, our model suggests that a weaker treatment may maintain enough coinfection to keep resistant viruses wrapped in susceptible capsids, while still maintaining low viral load.
The reason for this was due to the effectiveness of the treatment. As the treatment works, viral density collapses, coinfection plummets, and genotypes become linked to their phenotype. Resistant genomes are wrapped in their own proteins, and the drug now selects for them.
December 8, 2025 at 5:15 PM
The reason for this was due to the effectiveness of the treatment. As the treatment works, viral density collapses, coinfection plummets, and genotypes become linked to their phenotype. Resistant genomes are wrapped in their own proteins, and the drug now selects for them.
Adding a simple immune clearance step to our model and running out over multiple generations lets the model reproduce the pattern observed in the clinical trial, where late clearers predominantly had resistant infections.
December 8, 2025 at 5:15 PM
Adding a simple immune clearance step to our model and running out over multiple generations lets the model reproduce the pattern observed in the clinical trial, where late clearers predominantly had resistant infections.
At high density, viruses have a much higher rate of coinfection. Rare resistant genomes get packaged into capsids with lots of susceptible proteins. This means that the drug works well and resistance is suppressed.
December 8, 2025 at 5:15 PM
At high density, viruses have a much higher rate of coinfection. Rare resistant genomes get packaged into capsids with lots of susceptible proteins. This means that the drug works well and resistance is suppressed.
Our model captures the dynamics observed in cell culture, where coinfection with larger susceptible virus populations reduces resistant viral yield. We realized, however, that the MOI was quite large, and this was only a single round of passaging.
December 8, 2025 at 5:15 PM
Our model captures the dynamics observed in cell culture, where coinfection with larger susceptible virus populations reduces resistant viral yield. We realized, however, that the MOI was quite large, and this was only a single round of passaging.
So what gives? To investigate this discrepancy, we built an eco-evolutionary model for poliovirus treated by pocapavir and found that 𝐚 𝐬𝐢𝐧𝐠𝐥𝐞 𝐦𝐨𝐝𝐞𝐥 𝐜𝐨𝐮𝐥𝐝 𝐞𝐱𝐩𝐥𝐚𝐢𝐧 𝐛𝐨𝐭𝐡 𝐨𝐮𝐭𝐜𝐨𝐦𝐞𝐬.
December 8, 2025 at 5:15 PM
So what gives? To investigate this discrepancy, we built an eco-evolutionary model for poliovirus treated by pocapavir and found that 𝐚 𝐬𝐢𝐧𝐠𝐥𝐞 𝐦𝐨𝐝𝐞𝐥 𝐜𝐨𝐮𝐥𝐝 𝐞𝐱𝐩𝐥𝐚𝐢𝐧 𝐛𝐨𝐭𝐡 𝐨𝐮𝐭𝐜𝐨𝐦𝐞𝐬.
(Link to Collett et al.'s 2017 clinical trial here: doi.org/10.1093/infd...)
December 8, 2025 at 5:15 PM
(Link to Collett et al.'s 2017 clinical trial here: doi.org/10.1093/infd...)
However, clinical trials with pocapavir had mixed results. In 3/4 placebo-matched groups, pocapavir did not significantly reduce clearance time in people infected with OPV. Additionally, resistance evolved in nearly half of the experimental group, highly enriched compared to placebo.
December 8, 2025 at 5:15 PM
However, clinical trials with pocapavir had mixed results. In 3/4 placebo-matched groups, pocapavir did not significantly reduce clearance time in people infected with OPV. Additionally, resistance evolved in nearly half of the experimental group, highly enriched compared to placebo.
(Link to Tanner et al.'s 2014 fascinating study here: elifesciences.org/articles/03830)
December 8, 2025 at 5:15 PM
(Link to Tanner et al.'s 2014 fascinating study here: elifesciences.org/articles/03830)
A previous study by Tanner et al. showed the power of this phenomenon. They studied pocapavir, a capsid inhibitor that targets poliovirus. In coinfected cells, increasing amounts of susceptible viruses decreased resistant virus output, suggesting that resistance should be hard to evolve in PV.
December 8, 2025 at 5:15 PM
A previous study by Tanner et al. showed the power of this phenomenon. They studied pocapavir, a capsid inhibitor that targets poliovirus. In coinfected cells, increasing amounts of susceptible viruses decreased resistant virus output, suggesting that resistance should be hard to evolve in PV.
This leads to an interesting phenomenon that can be exploited by capsid inhibitors: resistant genomes can be wrapped with susceptible capsid subunits when resistant/susceptible genomes coinfect the same cell. This can dramatically mute selection for resistance.
December 8, 2025 at 5:15 PM
This leads to an interesting phenomenon that can be exploited by capsid inhibitors: resistant genomes can be wrapped with susceptible capsid subunits when resistant/susceptible genomes coinfect the same cell. This can dramatically mute selection for resistance.
First, some background. Most organisms have a direct link between their genotype and their phenotype. However, since viruses replicate inside of cells, different genotypes can co-occupy a cell and “share” their proteins with each other.
December 8, 2025 at 5:15 PM
First, some background. Most organisms have a direct link between their genotype and their phenotype. However, since viruses replicate inside of cells, different genotypes can co-occupy a cell and “share” their proteins with each other.
December 8, 2025 at 5:15 PM