Referral: MedCram On Avian Flu Mutations That Favor Human Transmission

[Michael Coston]

Referral: MedCram On Avian Flu Mutations That Favor Human Transmission

#18,445

As a blogger without a degree, I rely heavily on the skills and knowledge of others. One of the my favorite sources of reliable medical information is MedCram, which synthesizes important medical information (primarily for clinicians and medical students) into remarkably clear online lectures.

I've been a fan (and a subscriber) for years, and use it often just to bone up on medical topics I'm interested in. While they have a paid tier, they also have an extensive YouTube Channel with more than 1.5 million subscribers and over 550 of these presentations.​

Two weeks ago we learned that the critically ill teenager in British Columbia had been infected with the D1.1 genotype, which is similar to the genotype that infected > 12 poultry workers in Washington State.

A week ago, however, we learned that initial sequencing had revealed ambiguous mutations at several key sites (Q226 and E190) in the HA gene, although their significance - and when they occurred - wasn't clear.​

Yesterday Professor Roger Seheult, MD released a relatively short (12 min) review of what we know about the sequences from the B.C. case, titled: H5N1 Mutations Detected in Canadian Case Favor Human Transmission.

Highly recommended.
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We've not had an update from the B.C. Provincial Health officer Dr. Bonnie Henry on the condition of this teenager since Nov 12th, but there is a press briefing scheduled for this afternoon (2pm EST, 11am PST), where hopefully we'll learn more.

https://afludiary.blogspot.com/2024/11/referral-medcram-on-avian-flu-mutations.html​

 

[JJackson]

From the video, and comments, it seems there are SNIPs with significant impact on avian/mammalian binding affinity - HA 190 and 226. In this case there is no 100% consensus sequence at either site and I do not know the relative frequencies, but the options are E190D and Q226G or H. The E/D change is probably not significant, as the two amino acids are very similar. The change a 226, which is right at the heart of the RBS/sialic acid interaction, may well be important. Q226H looks the more interesting as it is a change from a polar uncharged side chain to positively charged one. The table in the video showing the binding impact of various 190 and 226 changes unfortunately does not include any of the options generated by this case, Q226R is listed, has +side chain and shifts the balance from a2-3 towards a2-6.
N.B. this is all guess work on my part, so take as-is, I would also add binding affinity may be a red herring as there is a lot more to virulence than cell entry. NS1 has a major impact on innate immunity, and there is always the host genetic variation and immunological response. Only if more cases with these changes occur will we know if the virulence is intrinsic to the virus or specific to this host.

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