Thread by @LauringLab

Teaching virus evolution to grad students tomorrow. Just reread the assigned paper. I think it's relevant to the discussion on immunocompromised hosts and VOC. Like most things COVID, we forget lessons from other viruses 1/x
journals.plos.org/plospathogens/…

Those who know me know that I love geeking out on within-host evolution and I love geeking out on poliovirus. So I will try to hold myself in check. Briefly, oral poliovirus OPV is live attenuated virus vaccine, so it replicates in gut and shed in stool. Thus, it evolves. 2/x

See recent work from @alvalesano @mt2fus @famulare_mike and others on this. It's long been recognized that individuals with primary immunodeficiencies related to antibody generation can have prolonged "infections" with OPV. 3/x
cell.com/cell-host-micr…

This paper reports what is probably the longest documented, 28 years. Phylogenetic tree (this person's samples in blue), molecular clock dates to roughly time of immunization. 4/x

Lots of amino acid substitutions in capsid (surface of virus, binds receptor, targeted by antibodies). More than typically seen in viruses recovered from individuals with polio. 5/x

These change antigenicity. This figure shows radial plots of ELISA with monoclonals, essentially mapping changes in targeted epitopes. 6/x

Here are mutations mapped to capsid structure. Red are the ones in antigenic sites. Many also outside of antigenic sites. So presumably selection is leading to antigenic changes and non-antigenic changes. Think about what those other selective pressures might be. 7/x

They also looked at how sera from individuals in the UK (where this case was) neutralize the wild type polio and OPV. Despite all these changes in the capsid and antigenic sites, people are still immune. 8/x

They also used a mouse model to look at how vaccination with IPV (the Salk inactivated vaccine, IM injection) protected against infection with viruses from this individual. Sera stimulated by IPV (cIPV here) protected against this wild type polio and virus from this patient. 9/x

I'll hold off on sharing all my interpretations (don't want blow the discussion in class tomorrow). But, I think you can see how this might affect how we interpret all the buzz about SARS-CoV-2 and IC hosts. 10/x

Here's link to article from @apoorva_nyc on this issue in SARS-CoV-2. 11/x
nytimes.com/2021/03/15/hea…