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Very interesting, thank you!

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Thanks for the deep and detailed analysis.

EBV seems like arguably the most successful virus in history: it infects 90% of one of the most viable species (lifespan X population) and persists for life.

A few questions if you don't mind:

1. Are you on Twitter?

2. I don't have access to paper 17. Did the reactivation occur in B cells or epithelial cells? Did they reveal the specific factors or signaling pathways for reactivation? It makes sense for EBV to reactivate when the immune system is stressed, but I want to learn more about the specific triggers.

3. To replicate cell lines, why can't you manufacture EBNA1 with mRNA technology and avoid the plasmid altogether?

4. You mention, "the rate of MS is about 15-fold lower in EBV-negative individuals compared to EBV-positive ones." What's the lower bound (roughly) for meaningfulness? For instance, would 5x be considered meaningful? 2x?

5. Why are anti-EBV antibodies mostly ineffective at preventing infection? Don't we have a clear understanding of EBV antigens?

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1. @Meta_Celsus but I don't tweet much

2. it's on Pubmed: https://www.ncbi.nlm.nih.gov/labs/pmc/articles/PMC8233978/

3. mRNA wouldn't be suitable here because you want the plasmid DNA to persist for strong, continued expression. (There are other cases where you can use mRNA though.)

4. I think 2x would be meaningful. There's actually new data showing it's more like 32X rather than 15X.

5. This is a good question, and I don't think it's fully understood. Yes, some antigens are important, but it's hard to get the body to make antibodies that neutralize EBV.

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* thanks for the reply. what's the best way to follow your work? are you on researchgate? will you announce posts on twitter? i'm esp interested in anything EBV related.

* you're saying without the plasmid, EBNA1 would not cause cell proliferation?

* is the antibody difficulty specific to EBV or is this a common issue with viral antigens?

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* how do we know EBV only infects humans? what properties allow it to infect only humans and not other mammals?

* what advantages does circular DNA afford EBV?

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