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In this answer on bioinformatics.stackexchange.com to the question inquiring about the validity of the paper Kristian G. Andersen et al, The proximal origin of SARS-CoV-2, the author asserts the following two points, which I do not understand.

  1. Serial passage of a virus through either animals will always attenuate the virulence, say the affinity to the ACE2 receptor, of the virus. My question: Could people artificially select for thus increase the virulence of the virus?

  2. We can always tell whether a virus is artificially serially passed because we know the mutational patterns of other serially passed viruses. My question: How does this distinguish artificial from natural passage?

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No. Serial passage through animals attenuate the virulence of a virus In It's ORIGINAL Host. it can cause and will cause an increased virulence in the animals that were used in serial passage, and, if the animals have similar receptors as humans, increase the virulence in humans as well. like the two experiments that passed bird flu across ferrets until they become virulent and airborne across them. https://www.cidrap.umn.edu/news-perspective/2014/04/experiments-render-h7n1-virus-more-contagious-ferrets https://www.scientificamerican.com/article/pandemic-bird-flu-studies-public/ https://science.sciencemag.org/content/336/6088/1534.full https://jvi.asm.org/content/88/12/6623

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  • $\begingroup$ +1. Any comments on the second question? $\endgroup$ – Hans May 3 at 19:36
  • $\begingroup$ It is hard to visualize but according to virologists passage into (mice) cells is very different to passage into (mice) lungs. The later greatly increases virulence (when the virus comes from another species) while the former is more likely to produce an attenuated vaccine strain. My opinion is that a last possibility, passage into cells then once adapted passage into lungs may produce a more virulent variant. @Hans $\endgroup$ – reuns May 4 at 20:07
  • $\begingroup$ @reuns: By "cells" do you mean in vitro, or tissue samples in a petri dish, and by "lungs" do you mean, in vivo, or lungs in a living animal? In the papers cited, the virus is first modified then serially passed in vivo amongst ferrets. ferrets have the human-like ACE2 receptor. By the way, do you know the reason for the large difference between passing in vitro and in vivo? I understand they are generally not equivalent. I am asking the reason about the large difference in this particular case $\endgroup$ – Hans May 4 at 20:33
  • $\begingroup$ In-vitro : immortalized cell lines. The exact process of SARS-CoV-2 passage into mice lungs is described in there. The 1st Wuhan institute of virology paper was showing that hela cells stopped to be susceptible when replacing human-ACE2 by mouse-ACE2, so the overall mechanism is quite complex. @Hans $\endgroup$ – reuns May 4 at 20:54
  • $\begingroup$ @reuns: Nice reference. This supports the answer negating the assertion of attenuating virulence. $\endgroup$ – Hans May 5 at 22:21

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