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Slack / Private Message Drop, pp.398-399 [SLACK_000612] · slack_pm:msg:04114

Date: 2021-01-14 14:38
Type: chat message · slack
recipient: Kristian G. Andersen, Robert F. Garry, Edward C. Holmes
speaker: Andrew Rambaut

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The convergence is possibly for cellular infectivity and immune evasion - all things that will be selected for in achronic infection without sterilising immunity. Strong competition between viruses for cells. However, my assumption has always been that this can only be likely to degrade transmissibility (given it was already transmissible at the beginning). But perhaps there is just a fortunate (for the virus) alignment of a within-host fitness peak and a between host one. And the latter involves too many intermediate steps with negative epistatic effects to reach in a stepwisefashion.

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2021-01-14 14:11 Kristian G. Andersen open

I still consider it MY (highly speculative!) hypothesis! MINE. MY HYPOTHESIS.
2021-01-14 14:18 Edward C. Holmes open

It's also in that ABC Australian podcast I did the other the day. But you can have it - I'm not 100% convinced yet. I'm not sure why evolution in individual chronic hosts will lead to convergent evolution for increased transmissibility atthe population scale. A few years ago we did a norovirus modelling study that said this sort of thing was unlikely, but that could easily be bollocks. https://academic.oup.com/ve/article/3/2/vex018/4055728
2021-01-14 14:27 Andrew Rambaut open

There is no evidence that there is increased transmissibility in either the Brazilian or South African strain.
2021-01-14 14:28 Andrew Rambaut open

It is clearly fit in the populations it is spreading in.
2021-01-14 14:38 Andrew Rambaut

The convergence is possibly for cellular infectivity and immune evasion - all things that will be selected for in achronic infection without sterilising immunity. Strong competition between viruses for cells. However, my assumption has always been that this can only be likely to degrade transmissibility (given it was already transmissible at the beginning). But perhaps there is just a fortunate (for the virus) alignment of a within-host fitness peak and a between host one. And the latter involves too many intermediate steps with negative epistatic effects to reach in a stepwisefashion.
2021-01-14 14:39 Andrew Rambaut open

Within host (and with the additional benefit of recombination) these combinations are readily obtainable.
2021-01-14 15:20 Edward C. Holmes open

Given the low frequency of chronic infections compared to the huge number with 'normal' durations of infection, doesn't the fact that we are seeing the same sort of constellation of mutations evolve and spread 3 times independently suggest that they have a major advantage at the population level?
2021-01-14 15:46 Andrew Rambaut open

Yes - they do. But I think they can't get there by progressive steps in sequential infections - there are troughs (wesee all of these mutations appear individually many times).
2021-01-14 15:47 Andrew Rambaut open

So the chronic infections offer an opportunity for these to arise in combination. Chronic infections are rare as aproportion of infections but there are shed loads of infections now.

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